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Law & Order is a franchise composed of a number of related American television series created by Dick Wolf.  They were originally broadcast on NBC, and all of them deal with some aspect of the criminal justice system. Together, the original series, its various spin-offs, the TV film, and crossover episodes from other shows constitute over 1,000 hours of programming.
Shared people and resources in a common fictional setting are the connecting links between the shows, e.g., Hudson University and the New York Ledger tabloid newspaper. Many supporting characters, such as district attorneys, psychologists, and medical examiners are also shared among the shows. Occasionally, crossovers of main characters or shared storylines between two of the shows will occur. A few major characters have also left the cast of one show within the franchise only to eventually join another. The music, style, and credits of the shows tend to be similar, with the voiceover in the opening of every series performed by Steven Zirnkilton.[1] The shows share the iconic "dun, dun" sound effect of a jail cell locking, created, along with the theme songs, by Mike Post.[2] Past episodes of the American series are in syndication with local over-the-air stations, along with cable channels such as USA Network and Bravo (both owned by the franchise's production company, NBCUniversal), TNT, WGN America, Ion Television, and AMC Networks' SundanceTV and WeTV, showing episodes sometimes up to six times a day.

In October 2012, Law & Order: Special Victims Unit show runner/executive producer Warren Leight said of the future of the Law & Order franchise, "(Dick Wolf and I) sometimes talk in general terms of where (the franchise) could go. I'm curious to see if there's another iteration somewhere down the line," he says. "We try hard to maintain a certain level of quality which I think is why the shows sustained in reruns so well. And I'd like to believe there's room for another generation in some way."[3] In February 2015, NBC was purported to have interest in bringing back the flagship Law & Order as a limited series.[4] As of February 2016, NBC has not publicly announced intentions to revive the original series.[5]
As of September27,2018, 1,131 original episodes of the Law & Order franchise have aired.
Series
Law & Order
20 seasons, 456 episodes (September 13, 1990 – May 24, 2010)
Law & Order, a crime procedural, features both a police investigation of a crime discovered during the cold open, and a prosecution case set forth by the New York County District Attorney, at the Manhattan DA's office. The first thirty minutes of an episode typically features a lead detective trio (in the final season, Jeremy Sisto, Anthony Anderson, and S. Epatha Merkerson), while the second thirty minutes follows their legal counterparts (in the final season, Alana de la Garza, Linus Roache, and Sam Waterston). On May 14, 2010, NBC announced that it was canceling the original series, although various spin-offs will continue. The series finale aired on May 24, 2010.[6] Wolf briefly attempted to continue the series on cable,[7][8] but the series "moved into the history books".[9]
Law & Order: Special Victims Unit
20 seasons, 444 episodes (September 20, 1999 – present)
SVU follows the cases investigated by Olivia Benson (Mariska Hargitay) and her Manhattan Special Victims Unit colleagues. The show's focus is on detectives who investigate sexually based crimes and crimes against children, the elderly, and women. As of the start of season twenty, these detectives include Kelli Giddish, Ice-T, and Peter Scanavino. Philip Winchester stars as his Chicago character Peter Stone.
Law & Order: Criminal Intent
10 seasons, 195 episodes (September 30, 2001 – June 26, 2011)
Criminal Intent focuses on high-profile cases investigated by the Major Case Squad, with special focus on the actions of the criminals pursued, often including scenes from the victim's or perpetrator's lives not involving the police, thereby giving a hint as to the "criminal intent". The detectives depicted, portrayed by Vincent D'Onofrio and Kathryn Erbe, during the final season, will often attempt to infiltrate the mind of the suspect. Julia Ormond and Jay O. Sanders also star in the tenth season of the series. On July 15, 2011, USA Network co-president Jeff Wachtel confirmed Law & Order: CI would end with its tenth season.[10]
Law & Order: Trial by Jury
1 season, 13 episodes (March 3, 2005 – January 21, 2006)
Trial by Jury, starring Bebe Neuwirth, Amy Carlson, and Jerry Orbach, followed the preparation by the legal teams, both prosecution and defense, for a jury trial. This was the first Law & Order spin-off to be canceled due to low ratings. Orbach's death (which occurred while the show was in production) was one factor to in the show's cancellation; competition from the hit series NUMB3RS was another.
Law & Order: LA
1 season, 22 episodes (September 29, 2010 – July 11, 2011)
Originally titled Law & Order: Los Angeles, LA was the first American Law & Order series set outside of New York City. As with the original series, the first half hour of the show focused on the police investigation of a crime discovered in the cold open; the second half took place at the Los Angeles County District Attorney's office and focused on the prosecution of the criminal suspect(s). On May 13, 2011, Law & Order: LA was canceled by NBC after only one season, but because of the hiatus did not air its final episode until July 11, 2011.[11][12][13] Alana de la Garza and Terrence Howard starred.
Law & Order True Crime
In April 2016, Wolf and NBC announced they were working on True Crime,[14] a scripted anthology series that will follow one significant true-to-life case per season. Season one, titled Law & Order True Crime: The Menendez Murders[15] stars Edie Falco as Leslie Abramson,[16] Gaston Villanueva as Lyle Menendez, and Gus Halper as Erik Menendez.[17] It premiered on September 26, 2017 and concluded its first season on November 14, 2017. The series is currently on hiatus.[18]
Law & Order: Hate Crimes
On September 4, 2018, NBC announced that it had given an order 13 episodes of the latest installment of the franchise entitled Law & Order: Hate Crimes.[19][20][21] Created by Wolf and Warren Leight, the series is based on the NYPD's actual Hate Crimes Unit which follows an elite team of specially trained investigators who investigate all forms of discrimination. The cast is set to be introduced in the latter part of the twentieth season of Special Victims Unit.
Media
TV film
The Law & Order franchise has one TV film, Exiled: A Law & Order Movie (1998). Chris Noth reprises his role as Mike Logan, as the film explores what happened to the character following his departure from the original series.
Video games
The franchise has also spawned a series of video games for the PC, which feature appearances by then-current cast members of the TV series.
The typical course of most of the games follows the original series' format with the player investigating a crime with interviews of witnesses and examination of evidence. After the arrest is made, the player then prosecutes the case with challenges such as selecting appropriate questions for witnesses on the stand, recognizing improper questions to raise objections and selecting the most persuasive arguments for the judge to allow certain evidence in court.
Law & Order: Dead on the Money
Law & Order: Double or Nothing
Law & Order: Justice Is Served
Law & Order: Criminal Intent
Law & Order: Legacies
Crossovers

The following table lists all the crossover stories in the Law & Order franchise.

John Munch crossovers

The character John Munch, who originated on Homicide, is notable for either appearing in or being referenced in a wide variety of other series, ranging from appearing in the science fiction series The X-Files, to the sitcom Arrested Development, to being referenced by name in the UK crime drama Luther. Whether this places these series in the Law & Order universe is a matter of debate.
Other related series
New York Undercover (1994–1998)
Co-created by Kevin Arkadie and Dick Wolf, NYU was implicitly a part of the same universe as the franchise, as psychologist and psychiatrist characters from L&O appeared in the series.
Deadline (2000–2001)
Also created by Dick Wolf, featured reporters based at the franchise's fictional newspaper, the New York Ledger.
Conviction (2006)
This series starred Stephanie March as Alexandra Cabot, Anson Mount as Jim Steele, Eric Balfour as Brian Peluso, J. August Richards as Billy Desmond, Milena Govich as Jessica Rossi, Julianne Nicholson as Christina Finn, and Jordan Bridges as Nick Potter. March reprises her role of Cabot originally from SVU and is now the Homicide Bureau Chief ADA. Cabot would return to SVU after this show's end. The series features a larger ensemble cast of young ADAs, with no police, therapists or medical examiners in lead roles. After its cancellation, two of the show's actresses, Milena Govich and Julianne Nicholson, went on to star in Law & Order and Law & Order: Criminal Intent respectively as Detectives Nina Cassidy and Megan Wheeler.
Foreign adaptations
The franchise, as a result of its popularity, has led to the adaptation of scripts from the American series into foreign-produced series. These are:
Paris enquêtes criminelles (Paris Criminal Investigations)
3 seasons, 20 episodes (May 3, 2007 – November 6, 2008)
Paris Criminal Investigations follows the format of Law & Order: Criminal Intent, adapted to Paris and the French legal system, with detectives from the Prefecture of Police DRPJ and  the Ministère public attempting to secure a conviction. The series stars Vincent Pérez, Sandrine Rigaux, Jacques Pater, Hélène Godec, Laure Killing, and Audrey Looten. The show is also aired in Germany on ZDF, under the title Law & Order: Paris.
Закон и Порядок. Отдел оперативных расследований (Law & Order:  Division of Field Investigations)
4 seasons, 84 episodes (2007–2011)
 Division of Field Investigations follows the format of Law & Order: Special Victims Unit, set in Moscow and adapted to the Russian justice system. The series stars Ivan Oganesyan, Alisa Bogart, Dmitry Brusnikin, Alexander Naumov, Valery Troshin and Xenia Entelis.
Закон и Порядок. Преступный умысел (Law & Order: Criminal Intent)
4 seasons, 84 episodes (2007–2011)
Criminal Intent follows the format of Law & Order: Criminal Intent, set in Moscow and is adapted to the Russian Justice System. The series stars Mikhail Homyakov, Igor Lagutin, Elena Kovalchuk and Boris Mironov.
Law & Order: UK
8 series, 53 episodes (February 23, 2009 – June 11, 2014)
UK follows the format of the original Law & Order show but adapts it to the new setting of London, with detectives from the Metropolitan Police CID and  the Crown Prosecution Service attempting to secure a conviction. The series stars Bradley Walsh, Jamie Bamber, Harriet Walter, Ben Daniels, Freema Agyeman, Bill Paterson, Paul Nicholls, Dominic Rowan, Georgia Taylor, Peter Davison, Sharon Small, Paterson Joseph, and Ben Bailey Smith.
Series overview

Location
Setting
Most of the American series have been filmed almost entirely in the New York City area. The original Law & Order series has filmed a few episodes in the Los Angeles area and Baltimore; these episodes or portions of episodes were set in the cities in which they were filmed and concerned multi-jurisdictional investigations or extradition.
Law & Order: Los Angeles expanded the franchise to a new main city, the new series' namesake. L&O: LA was canceled after one season.
Effects on casting
With some frequency, actors have appeared on the various series that make up the franchise, usually as different (sometimes very different) characters. This is because filming occurs in the New York City area and thus draws from the same pool of actors. Some prominent examples of the same actor playing different roles in different episodes are:
S. Epatha Merkerson playing a maid whose child was killed in a season 1 episode of the original L&O before joining the cast in season 4 as Lieutenant Anita Van Buren and going on to be the longest-serving cast member of the parent series.
Diane Neal playing a female rapist in an earlier season of Special Victims Unit before becoming the Assistant District Attorney for that series.
Annabella Sciorra playing a criminal defense attorney in Trial by Jury and later Det. Mike Logan's (Chris Noth) partner in Criminal Intent
Jerry Orbach playing a defense attorney on the original series before joining it as Det. Lennie Briscoe
Ice-T playing a pimp known as Seymour Stockton in the franchise's only film, Exiled: A Law & Order Movie, before taking on the role of Tutuola on SVU
Anthony Anderson playing Detective Lucius Blaine in a seventh-season episode of SVU before playing Bernard on the original Law & Order
Jeremy Sisto played a defense attorney in the last episode of season 17 before joining the cast as Cyrus Lupo at the start of season 18.
Kelli Giddish played a rape victim in the eighth-season episode "Outsider" of SVU before joining the show in season 13 as Amanda Rollins.
Raúl Esparza played different characters on Law & Order and Criminal Intent before joining SVU in its 14th season as Assistant District Attorney Rafael Barba.
Peter Scanavino playing multiple characters in Law & Order, Criminal Intent, Trial by Jury and SVU before joining the last in season 16 as Dominick Carisi.
Also due to the New York filming, a number of actors appearing in  Law & Order shows have had regular or recurring roles on soaps. Most notable is Tamara Tunie, who simultaneously played both medical examiner Melinda Warner on SVU as well as (until 2007) District Attorney Jessica Griffin on As the World Turns. Likewise, New York theater actors have also been frequently cast.
Also as the result of sharing the same pool of New York-based television actors, the series' casts have had significant overlap with that of the former HBO series Oz. This is perhaps most pronounced in Law & Order: Special Victims Unit, whose cast has included three regularly credited actors (Christopher Meloni, BD Wong and Dean Winters), as well as two recurring actors (J.K. Simmons and Mike Doyle) who were also regularly credited actors on Oz, also Kathryn Erbe from Oz starring in Law & Order: Criminal Intent.  Similarly, Law & Order: UK sees significant overlap with other programs' casts; most prominently series regulars Freema Agyeman and Peter Davison, who starred in Doctor Who as companion Martha Jones and the Fifth Doctor.
Characters in the franchise

Police

Prosecutors

Medical professionals

Abbreviations

True Crime

How many series of Law & Order are there?


Pilot certification in the United States is typically required for an individual to act as a pilot-in-command of an aircraft. It is regulated by the Federal Aviation Administration (FAA), a branch of the U.S. Department of Transportation (USDOT). A pilot is certified under the authority of Parts 61, under 141 of Title 14 of the Code of Federal Regulations (if training was conducted by an FAA-approved school), also known as the Federal Aviation Regulations (FARs), or under part 107 rules for  drone operation.
An FAA-issued pilot certificate is evidence that an individual is duly authorized to exercise piloting privileges. The pilot certificate is one of several kinds of airman certificates issued by the FAA.
General structure of certification
A pilot is certificated to fly aircraft at one or more named privilege levels and, at each privilege level, rated to fly aircraft of specific categories. Privilege levels of pilot certificates are, in order of increasing privilege:[1]
Student Pilot: an individual who is learning to fly under the tutelage of a flight instructor and who is permitted to fly alone under specific, limited circumstances
Sport Pilot: an individual who is authorized to fly only Light-sport Aircraft
Remote Pilot: an individual who may fly small Unmanned Aerial Vehicles (UAV) for compensation or hire
Recreational Pilot: an individual who may fly aircraft of up to 180 horsepower (130kW) and 4 seats in the daytime for pleasure only
Private Pilot: an individual who may fly for pleasure or personal business, generally without accepting compensation
Commercial Pilot: an individual who may, with some restrictions, fly for compensation or hire
Airline Transport Pilot (often called ATP): an individual authorized to act as pilot for a scheduled airline.  (First Officers that fly under 14CFR 121 are required to hold an Airline Transport Pilot Certificate as of August 1, 2013.)

Pilots can be rated in these aircraft categories:[1][2]
Airplane
Rotorcraft
Glider
Lighter than air
Powered lift
Powered parachute
Weight-shift control
Most aircraft categories are further broken down into classes.  If a category is so divided, a pilot must hold a class rating to operate an aircraft in that class:[1]
The Airplane category is divided into single-engine land (ASEL), multi-engine land (AMEL), single-engine sea (ASES), and multi-engine sea (AMES) classes
The Rotorcraft category is divided into helicopter and gyroplane classes
The Lighter-than-air category is divided into airship and balloon classes
The Powered parachute category is divided into powered parachute land and powered parachute sea
The Weight-shift-control category is divided into weight-shift-control land and weight-shift-control sea
A student pilot certificate does not list category or class ratings but is instead endorsed by a flight instructor to confer privileges in specific makes and models of aircraft.
A type rating is required in a specific make and model of aircraft if the aircraft weighs more than 12,500lb (5,700kg) at takeoff or is powered by one or more turbojet engines. The Boeing 747, Beechcraft Super King Air 350, and the Hawker Hunter are examples of aircraft that require type ratings.[1]
To legally operate under instrument flight rules (IFR), a pilot can separately add an instrument rating to a private or commercial certificate. An airline transport pilot implicitly holds an instrument rating, so the instrument rating does not appear on an ATP certificate. The FAA issues instrument ratings separately for airplane and powered lift categories and the helicopter class (INSTA and INSTH).[1] Glider and airship pilots may also operate under Instrument Flight Rules under certain circumstances.[3] An individual may hold only one pilot certificate at one time; that certificate may authorize multiple privilege levels distinguished by aircraft category, class or type. For example, an Airline Transport Pilot certificate holder may be permitted to exercise ATP privileges when flying multi-engine land airplanes, but only Commercial Pilot privileges when flying single-engine land airplanes and gliders.  Similarly a Commercial Pilot holder with a glider rating may have only Private Pilot privileges for single-engine land airplanes.
The FAA may impose limitations on a pilot certificate if, during training or the practical test, the pilot does not demonstrate all skills necessary to exercise all privileges of a privilege level, category, class or type rating.  For example, a holder of a DC-3 type rating who does not demonstrate instrument flying skills during the practical test would be assigned a limitation reading, "DC-3 (VFR Only)".
To obtain a certificate or add a rating, a pilot usually has to undergo a course of training with a Certificated Flight Instructor (CFI) under 14CFR61 or enroll at an approved course at a 14CFR141 approved flight school.  The applicant must accumulate and log specific aeronautical experience, and pass a three-part examination: a knowledge test (a computerized multiple-choice test, typically called the "written test"), an oral test, and a practical test carried out by either an FAA inspector or a Designated Pilot Examiner.
Another form of authorization is a logbook endorsement from a flight instructor that establishes that the certificate holder has received training in specific skill areas that do not warrant a full test, such as the ability to fly a tailwheel-equipped, high-performance, complex, or pressurized airplane.
Pilot certificates do not expire, although they may be suspended or revoked by the FAA.[4] However, a pilot must maintain currency — recent flight experience that is relevant to the flight being undertaken. To remain current, every pilot has to undergo a flight review with an instructor every 24 calendar months unless she or he gains a new pilot certificate or rating in that time or satisfies the flight review requirement using an alternate approved means. For most types of certificate, she or he must also undergo a medical examination at intervals ranging from six months to five years, depending on the pilot's age and desired flight privileges. Other currency requirements apply to the carriage of passengers or to flight under instrument flight rules (IFR).
A medical certificate is not necessary to fly a glider, balloon, or light-sport Aircraft. An ultralight aircraft may be piloted without a pilot certificate or a medical certificate.
In addition to pilot certificates, the FAA issues separate airman certificates for Flight Engineers, Flight Instructors, Ground Instructors, Aircraft Dispatchers, Mechanics, Repairmen, Parachute Riggers, Control Tower Operators, Flight Navigators, and Flight Attendants.[5]
Pilot training
Most pilots in the U.S. undergo flight training as private individuals with a flight instructor, who may be employed by a flight school. Those who have decided on aviation as a career often begin with an undergraduate aviation-based education. Some pilots are trained in the military and are issued with civilian certificates based on their military record. Others are trained directly by airlines. The pilot may choose to be trained under Part 61 or Part 141 of the FARs. Part 141 requires that a certificated flight school provide an approved, structured course of training, which includes a specified number of hours of ground training (for example, 35 hours for Private Pilot in an airplane). Part 61 sets out a list of knowledge and experience requirements, and is more suitable for students who cannot commit to a structured plan, or for training from freelance instructors. Under Part 61 pilot training, individuals can become a private pilot in about three months and a commercial pilot in as quick as seven months.[6]
Knowledge tests
Most pilot certificates and ratings require the applicant to pass a knowledge test, also called the written test. The knowledge test results are valid for a period of 2 years, and are usually a prerequisite for practical tests. Resources available to prepare for the knowledge test may be obtained from pilot supply stores or vendors. The exceptions where a knowledge exam is not required for a practical test are for some add-on ratings after the initial license, such as a powered aircraft pilot adding another category rating at the same license level.[7]
To take knowledge tests for all pilot certificates and ratings, the applicant must have a sign-off from a ground or flight instructor. These are usually given by an instructor who has taught a ground school course, provided ground instruction or reviewed the applicant's self-study preparations. Certain circumstances don't require sign-offs for some flight instructor or airline transport pilot knowledge tests.
Practical tests
All pilots certificates and ratings require a practical test, usually called a check ride. For each practical test, the FAA publishes a Practical Test Standards document that they expect the applicant to study, the flight instructor to teach and evaluate against, and the examiner to use to conduct the exam. A practical test is administered by an FAA Inspector or an FAA Designated Pilot Examiner. The check-ride is divided into two parts: the oral exam followed by a flight test in the aircraft. Upon successful completion of the practical test, the examiner issues a temporary airman certificate with the new license or rating. To take practical tests for all pilot certificates and ratings (except airline transport pilot), the applicant must have proper logbook endorsements from their flight instructor.
Becoming a professional pilot
In aviation, a pilot's level of income and experience are closely related. There are multiple ways to gain the experience required for hire by a scheduled air carrier. Air carriers generally require that the pilots they hire have hours of experience far in excess of the legal minimum. Effective August 1, 2013, all airline pilots must have an Airline Transport Pilot Certificate (ATP) or an Airline Transport Pilot Certificate with restricted Privileges (ATP-r). An ATP allows a pilot to act as the Captain or First Officer of an airline flight and requires 1,500 hours of total flight time as well as other requirements (i.e. 25 hours of night, 23 years old), see .  An ATP-r certificate allows a pilot to act as a First Officer in a two pilot crew if they do not meet certain requirements. For example, the total flight time requirement is reduced to as little as 750 hours and the age requirement is reduced to 21.  .
Experience is often gained using these methods:
Military training (because of increased retention efforts by the military services and reduced numbers of active pilots, this is no longer a major source of pilots entering civilian careers),
Independent training followed by becoming a part- or full-time instructor.
A college-level aviation program, in which a bachelor's degree (commonly in Aviation Science or a related field) is conferred upon the completion of both flight and classroom coursework. Frequently, upperclassmen are employed as flight instructors for other students.
Banner towing, traffic reporting, skydiver pilot, fire patrol, pipeline patrol, aerial photography, glider towing, or other "odd jobs" in aviation are fairly low-paying and require only the legal minimum experience.  Reaching the regulatory 1,200 hour flight time minimum to act as pilot-in-command under Part 135 on-demand operations is a common means of gaining experience in line operations, weather flying, etc., leading to passenger airline jobs.
Pilot certificates
The FAA offers a progression of pilot certificates or licenses. Each license has varying experience and knowledge requirements and has varying privileges and limitations.
Student pilot
A student pilot certificate is obtained through the FAA's Integrated Airman Certification and Rating Application (IACRA) system.[8] The student pilot certificate is only required when exercising solo flight privileges. Student pilots must also possess a medical certificate when conducting flights requiring medical certification.  As of April 1, 2016 student pilot certificates do not expire.  Once a student has accrued sufficient training and experience, a CFI can endorse the student's logbook to authorize limited solo flight in a specific type (make and model) of aircraft. Additional endorsements must be logged for specific airports where a student operates solo.
There is no minimum aeronautical knowledge or experience requirement for the issuance of a student pilot certificate. There are, however, minimum aeronautical knowledge and experience requirements for student pilots to solo, including:[9]
Solo requirements:
Be at least 16 years of age (14 for glider or balloon)
Read, speak, write, and understand the English language.
Demonstrate satisfactory aeronautical knowledge on a knowledge test, including knowledge of the following areas:
Airspace rules and procedures for the airport where the solo flight is performed
Flight characteristics and operational limitations for the make and model of aircraft to be flown
Receive and log flight training for the maneuvers and procedures appropriate to the make and model of aircraft to be flown, including:
Preflight preparation
Taxiing or surface operations, including run-ups
Takeoffs and landings, including normal and cross-wind
Straight and level flight, and turns in both directions
Climbs and climbing turns
Airport traffic patterns, including entry and departure procedures
Collision avoidance, wind shear avoidance, and wake turbulence avoidance
Descents, with and without turns, using high and low drag configurations
Flight at various airspeeds from cruise to slow flight
Stall entries from various flight attitudes and power combinations with recovery initiated at the first indication of a stall, and recovery from a full stall
Emergency procedures and equipment malfunctions
Ground reference maneuvers
Approaches to a landing area with simulated engine malfunctions
Slips to a landing
Go-arounds
Limitations while flying solo:
May not carry passengers.
May not fly for hire or in furtherance of a business.
May not fly in other than VMC or above clouds when visual reference cannot be made to the surface.
May not fly contrary to limitations placed in logbook by instructor.
Sport pilot
The sport pilot certificate was created in September 2004 .The intent of the new rule was to lower the barriers of entry into aviation and make flying more affordable and accessible.
The new rule also created the Light Sport Aircraft (LSA) category of aircraft, which are smaller, lower-powered aircraft.  The sport pilot certificate offers limited privileges mainly for recreational use. It is the only powered aircraft certificate that does not require a medical certificate; a valid vehicle driver's license can be used as proof of medical competence provided the prospective pilot was not rejected for their last Airman Medical Certificate.
Before a trainee can start the solo phase of flight training, a Student Sport Pilot Certificate must be issued by the Federal Aviation Administration (FAA). These may be obtained from an FAA Flight Standards District Office or FAA Designated Pilot Examiner.
To qualify for the sport pilot certificate, an applicant must:[10]
Be at least 16 years of age (14 for glider or balloon)
Be able to read, speak, write, and understand English
Log at least 20 hours of flight time, of which at least
15 hours must be dual instruction with a qualified flight instructor
2 hours must be cross-country dual instruction
5 hours must be solo flight
Fly one solo cross-country flight over a total distance of 75 or more nautical miles to two different destinations to a full-stop landing.  At least one leg of this cross-country must be over a total distance of at least 25 nautical miles (46km).
Have received 2 hours of dual instruction in the preceding 60 days, in preparation for the Practical Test
Pass a Knowledge (written) test
Pass a Practical (oral and flight) test
Have a valid US State drivers license or a current 3rd class or higher Airman Medical Certificate
The above requirements are for heavier-than-air powered aircraft (airplanes).  The requirements for gliders, balloons, gyroplanes, and dirigibles vary slightly.
Sport pilots are only eligible to fly aircraft that are either certificated specifically as light-sport aircraft (LSA) or were certificated prior to the LSA regulations and are within the maximum weight and performance limitations of light-sport aircraft.
The restrictions placed on a Pilot exercising the privileges of a Sport pilot certificate are:
No more than one passenger
Daytime flight only (civil twilight is used to define day/night)
Maximum Takeoff Weight of 1320lbs,[11] compared to 12,500lb (5,700kg) of the Private Pilot Certificate or the Recreational Pilot Certificate.
No flight above 10,000 feet (3,000m) MSL or 2,000 feet (610m) AGL, whichever is higher (this automatically excludes flight in Class A airspace)
No flight in any of the airspace classes that require radio communication (B, C, or D) without first obtaining additional instruction and instructor endorsement
The Sport pilot certificate is also ineligible for additional ratings (such as an Instrument rating), although time in light-sport aircraft can be used towards the experience requirement of other ratings on higher certificate types.
Recreational pilot
The recreational pilot certificate requires less training and offers fewer privileges than the private pilot certificate. It was originally created for flying small single-engine planes for personal enjoyment; the newer Sport Pilot certificate overlaps this need and is easier to get, but the recreational certificate allows access to larger single-engine aircraft, and instructor endorsements are available to recreational pilots that are not applicable to sport pilots, such as flying at night or cross-country.
Eligibility requirements:
Be at least 17 years old
Be able to read, speak, write and understand the English language
Pass a required knowledge test
Pass a required oral and practical flight test administered by a FAA designated examiner
Hold either a student or sport pilot certificate.[12]
Meet the following experience requirements:
30 hours of flight time (15 hours of flight training, 3 hours of solo time, 2 hours of cross country > 25NM)[13]
Limitations and restrictions (without additional endorsement):
May not carry more than one passenger.
May not fly to an airport further than 50nmi from the departure point.
May not fly in Class B, C, D airspace or to any controlled airport.
May not fly an aircraft that has more than four seats, a tailwheel, more than one engine, or more than 180hp.
May not fly aircraft falling under the definition of a complex airplane, with retractable gear, adjustable flaps and variable-pitch propeller.
May not fly between sunset and sunrise.
May not fly above 10,000ft MSL or 2,000ft AGL (whichever is higher)[14]
If pilot has logged less than 400 hours and has not acted as pilot in command within 180 days, a flight review is required prior to any flight without an instructor.
Most of the above limitations, except the one-passenger, four-seat and single-engine restrictions, can be relaxed or lifted individually through instructor endorsement. These endorsements are obtained by participating in a prescribed course of ground and/or flight instruction given by an FAA-certificated instructor, including a minimum number of instructor-led flight in a plane or situation normally requiring the endorsement. Common types of endorsement for recreational pilots can allow:
Taking off from and landing at controlled airports and flying within their Class B/C/D airspace.
Command of "complex airplanes" with mechanisms or flight systems including retractable gear, flaps, and variable-pitch propellers.
Command of "high-performance" aircraft with engine ratings in excess of 180hp.
Command of pressurized aircraft at altitudes exceeding 10,000 MSL (but not above FL180).
Command of tailwheel aircraft (many such designs are WWII-era fighters which usually also require "complex" and "high-performance" endorsements).
Command of a specific make and model of aircraft, regardless of its capabilities.
The aircraft endorsed must still be single-engined and have four or fewer seats; a recreational pilot may be endorsed for a Mooney Bravo or even a P-51 without having general endorsements for high-performance, complex or tailwheel aircraft, but cannot be endorsed to fly a six-seat Cessna 206 or twin-engine Piper Aztec.
Flights beyond 50NM from the departure point, including cross-country VFR flying.
Night flying by VFR (an instrument rating is still required for night SVFR/IFR, and practically requires a private pilot certification)
A recreational pilot will typically only get a few of these, to allow operation of an aircraft in a few exceptional situations applicable to their locale (the Class B/C/D endorsement, for instance, is practically required for pilots living in major cities). Pilots requiring a large subset of these endorsements are typically better served by obtaining their private pilot certification.

Private pilot
The private pilot certificate is the certificate held by the majority of active pilots. It allows command of any aircraft (subject to appropriate ratings) for any non-commercial purpose, and gives almost unlimited authority to fly under visual flight rules (VFR). Passengers may be carried and flight in furtherance of a business is permitted; however, a private pilot may not be compensated in any way for services as a pilot, although passengers can pay a pro rata share of flight expenses, such as fuel or rental costs. Private pilots may also operate charity flights, subject to certain restrictions, and may participate in similar activities, such as Angel Flight, Civil Air Patrol and many others.
The requirements to obtain a private pilot certificate for "airplane, single-engine, land", or ASEL, (which is the most common certificate) are:[15]
Be at least 17 years old (16 years old for glider or balloon rating) [16]
Be able to read, speak, write and understand the English language
Obtain at least a third class medical certificate from an Aviation Medical Examiner (except for glider or balloon)
Pass a computerized aeronautical knowledge test
Accumulate and log a specified amount of training and experience, including the following:
If training under Part 61, Title 14 of the Code of Federal Regulations (CFR) section 61.109, requires at least 40 hours of flight time, including 20 hours of flight with an instructor and 10 hours of solo flight (i.e., by yourself), and other requirements including cross-country flight, which include
Solo requirements:
5 hours of solo cross-country time
One solo cross-country flight of at least 150nmi (280km) total distance, with full-stop landings at a minimum of three points and with one segment of the flight consisting of a straight-line distance of at least 50nmi (93km) between the takeoff and landing locations
Three solo takeoffs and landings to a full stop at an airport with an operating control tower.
Night requirements:
3 hours of night flight training
10 takeoffs and 10 landings to a full stop (with each landing involving a flight in the traffic pattern) at an airport
1 cross country flight of 100nm total distance at night
3 hours of flight training on the control and maneuvering solely by reference to instruments
3 hours of flight training for cross country flights
3 hours of flight training with an authorized instructor in preparation for the practical test, which must have been performed within the preceding 2 calendar months from the month of the test
If training under Part 141, at least 35 hours of piloting time including 20 hours with an instructor and 5 hours of solo flight, and other requirements including cross-country and night flights
Pass an oral test and flight test administered by an FAA inspector, FAA-designated examiner, or authorized check instructor
Commercial pilot
A certificated commercial pilot may act as pilot-in-command of an aircraft for compensation or hire, as well as carry persons or property for compensation or hire.[17] Training for the certificate focuses on a better understanding of aircraft systems and a higher standard of airmanship.[18]  The commercial certificate itself does not allow a pilot to fly in instrument meteorological conditions.  For aircraft categories where an instrument rating is available, commercial pilots without an instrument rating are restricted to daytime flight within 50 nautical miles (93km) when carrying passengers for hire.[19]
A commercial airplane pilot must be able to operate a complex airplane, as a specific number of hours of complex (or turbine-powered) aircraft time are among the prerequisites.
The requirements are:
Be at least 18 years of age
Hold a private pilot certificate
Be able to read, speak, write, and understand the English language
Accumulate and log a specified amount of training and experience; the following are part of the airplane single-engine land class rating requirements:
If training under Part 61, at least 250 hours of piloting time including 20 hours of training with an instructor and 10 hours of solo flight, and other requirements including several "cross-country" flights, i.e., more than 50 nautical miles (93km)(25 NM for helicopter rate)  from the departure airport (which include Day VFR and Night VFR 100nmi (190km) between beginning point and destination, with a time of at least two hours; also one cross country of at least 250nmi (460km) to the destination, a 300nmi (560km) total distance, with landings at three airports) and both solo and instructor-accompanied night flights
If training under Part 141, at least 150 hours of training time including 55 hours with an instructor and 10 hours of solo flight, and other requirements including several cross-country, solo, and night flights
Pass a 100-question aeronautical knowledge written test
Pass an oral test and flight test administered by an FAA inspector, FAA-designated examiner, or authorized check instructor
By itself, this certificate does not permit the pilot to set up an operation that carries members of the public for hire; such operations are governed by other regulations. Otherwise, a commercial pilot can be paid for certain types of operation, such as banner towing, agricultural applications, and photography, and can be paid for instructing if she or he holds a flight instructor certificate (In the case of lighter-than-air, only a commercial pilot certificate is required to teach for that category). To fly for hire, the pilot must hold a second class medical certificate, which is valid for 12 months.[20]
Often, the commercial certificate reduces the pilot's insurance premiums, as it is evidence of training to a higher safety standard.
Airline transport pilot
An airline transport pilot (commonly called an "ATP") is tested to the highest level of piloting ability. The certificate is a prerequisite for acting as a flight crew-member in scheduled airline operations.
The minimum pilot experience is 1,500 hours of flight time (1200 for Helicopters), 500 hours of cross-country flight time, 100 hours of night flight time, and 75 hours instrument operations time (simulated or actual). Other requirements include being 23 years of age, an instrument rating, being able to read, write, speak, and understand the English language, a rigorous written examination, and being of good moral character.[21]
An Airline Transport Pilot - restricted (ATP-r) is also available for pilots that do not meet the more rigorous requirements of an ATP.  The only hour requirement for the ATP-r is 1,500 total and 200 cross country.  The "total time" requirement is reduced to 750 hours for former military pilots, 1,000 hours for graduates of university bachelor's degree programs, or 1,250 for graduates of university associate degree programs.  The holder of an ATP-r is limited to only serving as the First Officer in a two pilot operation.  Upon obtaining the requisite age and aeronautical experience, the pilot is issued an unrestricted ATP without further examination.   and
Remote pilot
UAV's weighting between more than 0.55 lbs and less than 55 lbs[22] or used in a commercial nature is subject to part 107 regulations. Exemptions for part 107 are granted on a case by case basis by the FAA subject to risk mitigation[23]. UAV weighting 55 lbs or more are subject to part 333 regulations[24].

Eligibility requirements[25][26]:

(Non part 61 certificate holders)
Be at least 16 years old
Be able to read, speak, write and understand the English language
Pass a required knowledge test
Must be easily accessible by the remote pilot during all UAS operations
Valid for 2 years – certificate holders must pass a recurrent knowledge test every two years
(Part 61 certificate holders)
Must hold a pilot certificate issued under 14 CFR part 61
Must have completed a flight review within the previous 24 months
Valid for 2 years – certificate holders must pass either a recurrent online training course OR recurrent knowledge test every two years

Restrictions [27]
Unmanned aircraft must weigh less than 55 lbs. (25 kg).
Visual line-of-sight (VLOS) only; the unmanned aircraft must remain within VLOS of the remote pilot in command and the person manipulating the flight controls of the small UAS. Alternatively, the unmanned aircraft must remain within VLOS of the visual observer.
At all times the small unmanned aircraft must remain close enough to the remote pilot in command and the person manipulating the flight controls of the small UAS for those people to be capable of seeing the aircraft with vision unaided by any device other than corrective lenses.
Small unmanned aircraft may not operate over any persons not directly participating in the operation, not under a covered structure, and not inside a covered stationary vehicle.
Daylight-only operations, or civil twilight (30 minutes before official sunrise to 30 minutes after official sunset, local time) with appropriate anti-collision lighting.
Must yield right of way to other aircraft.
May use visual observer (VO) but not required.
First-person view camera cannot satisfy “see-and-avoid” requirement but can be used as long as requirement is satisfied in other ways.
Maximum groundspeed of 100 mph (87 knots).
Maximum altitude of 400 feet above ground level (AGL) or, if higher than 400 feet AGL, remain within 400 feet of a structure.
Minimum weather visibility of 3 miles from control station (500 feet of visibility below clouds, and 2000 feet horizontally away from clouds)[28].
Operations in Class B, C, D and E airspace are allowed with the required ATC permission.
Operations in Class G airspace are allowed without ATC permission.
No person may act as a remote pilot in command or VO for more than one unmanned aircraft operation at one time.
No operations from a moving aircraft.
No operations from a moving vehicle unless the operation is over a sparsely populated area.
No careless or reckless operations.
No carriage of hazardous materials.
Flying UAS in and around stadiums is prohibited starting one hour before and ending one hour after the scheduled time of any of the following events (Specifically, UAS operations are prohibited within a radius of three nautical miles of the stadium or venue.)[29]:
Major League Baseball
National Football
It is possible to mix the license levels on one certificate.  For example, a private pilot with both glider and airplane ratings could earn a commercial license for gliders.  The new license would then list the airplane ratings as having only "private privileges."
Number of active pilots
As of the end of 2017, in the US, there were an estimated 609,306 active certificated pilots.[30]  This number has been declining gradually over the past several decades, down from a high of over 827,000 pilots in 1980.  There were 702,659 in 1990 and 625,581 in 2000.  The numbers include:
120,546 student pilots (128,663 in 1990 and 93,064 in 2000)
220 recreational pilots (87 in 1990 and 340 in 2000)
5,157 sport pilots (did not exist until 2005)
174,883 private pilots (299,111 in 1990 and 251,561 in 2000)
104,322 commercial pilots (149,666 in 1990 and 121,858 in 2000)
152,933 airline transport pilots (107,732 in 1990 and 141,596 in 2000)
19,927 glider-only pilots (9,567 in 1990 and 7,775 in 2000)
15,511 rotorcraft-(helicopter)-only pilots (7,833 in 1990 and 9,387 in 2000)
554,177 male pilots end of 2014
39,322 female pilots end of 2014
These numbers are based on the highest certifications held by individual pilots.
The numbers also include:
100,993 certificated flight instructors (CFIs) (63,775 in 1990 and 80,931 in 2000)
306,066 pilots overall who held instrument ratings (297,073 in 1990 and 311,944 in 2000)
An active pilot is defined as one who holds both a pilot certificate and a valid medical certificate, for certifications that require a medical certificate.
Other certificates and ratings
A flight instructor certificate authorizes the holder to give training and endorsement for a certificate, and perform a flight review.
A Ground Instructor Certificate authorizes the holder to give ground instruction, give knowledge exam endorsements, and provide the ground training portion of a flight review.[31]
An instrument rating is required to fly under instrument flight rules. Instrument ratings are issued for a specific category of aircraft; a pilot certificated to fly an airplane under IFR has an Instrument Airplane rating.
An instrument instructor rating authorizes a certificated flight instructor to give training and endorsement for an instrument rating pilot.
A multi-engine rating is required to fly an airplane with more than one engine. It is the most common example of a class rating.
A multi-engine instructor rating authorizes a certificated flight instructor to give training and endorsement for a multi-engine rating.
United States military pilots are issued an Aviator Badge upon completion of flight training and issuance of a pilot's certificate.  Badges for crew or ground positions are also issued to qualified applicants.
Unmanned Aircraft System (Drone) pilots are required to obtain a remote pilot airman certificate with a small UAS rating when operating commercially.
Medical certification and requirements
All certificated pilots, with the exception of those with a sport or Recreational pilot certificate[32] (or when in command of balloons or gliders, including power assisted gliders), are required to maintain a medical certification commensurate with the privileges they intend to exercise as pilot-in-command of an aircraft.
For sport pilot certificate applicants or holders, regulations state that a medical is required if the applicant/pilot does not hold a valid United States drivers license.
To obtain a medical certification, pilots are required to undergo a medical examination from an Aviation Medical Examiner, or AME. The Aviation Medical Examiner performs an examination based upon the class of certification desired.
Medical certifications are divided into three classes:
Third class
Third class certifications require the least involved examinations of all medical certifications. They are required for those intending to be pilot-in-command of an aircraft under the Private or Recreational pilot certificates or while exercising solo privileges as a student pilot.
To qualify for a third class medical certificate, pilots must meet the following requirements:
Distant vision: 20/40 or better in each eye separately,[33] with or without correction
Near vision: 20/40 or better in each eye separately, with or without correction, as measured at a distance of 16 inches (410mm)
Color vision: Demonstrate the ability to perceive the colors necessary for the safe performance of airman duties
Hearing: Demonstrate the ability to hear an average conversational voice in a quiet room, using both ears, at a distance of six feet, with their back turned to the examiner, or pass an approved audiometric test
Ear, Nose, and Throat: Exhibit no ear disease or condition manifested by, or that may reasonably be expected to be manifested by, vertigo or a disturbance of speech or equilibrium
Blood Pressure: Under 155/95
Mental Status: No diagnosis of psychosis, bipolar disorder, or severe personality disorders
Substance Dependence: No dependence on alcohol or any pharmacological substance in the previous two years
For pilots under 40 years of age, third class medical certificates expire on the last day of the month they were issued, five years from the date of issue. The FAA changed this rule from three to five years on July 24, 2008.[34][35] For all others, they expire on the last day of the month they were issued, two years from the date of issue.
In December 2015, the U.S. Senate passed a bill sponsored by Montana Senator Steve Daines, S. 571- Pilot's Bill of Rights 2 (PBOR 2). If signed into law, the bill would expand the third class medical exemption for recreational pilots by reforming the FAA's medical certification process to include more qualified, trained pilots.[36][37]
Second class
A second class medical is required for those intending to exercise the privileges of the commercial pilot certificate.  It is possible to obtain a commercial pilot certificate while holding a third class medical, but with the exception of flight instruction, the licensee cannot exercise privileges beyond that of a private pilot.
To qualify for a second class medical certificate, pilots must meet the requirements for the third class certificate plus:
Distant vision: 20/20 or better in each eye separately, with or without correction
Intermediate vision: 20/40 or better in each eye separately, with or without correction, at age 50 and over, as measured at 32inches
Second class certificates are valid until the last day of the month, twelve months after they were issued. The certificate holder may then only exercise the privileges of a third class medical certificate.
First class
First class certificates are required for those intending to be pilot-in-command in an air carrier operation requiring an Airline Transport Pilot (ATP) certificate. Other operations, including those under Part 91, may require a first class medical for insurance purposes, although it is not a federal requirement in such cases.
To qualify for the first class medical certificate, pilots must meet the requirements for the third and second class certificates plus:
Heart Function: Electrocardiogram must show normal heart function once at age 35 and annually for those age 40 and over
For pilots under 40 years of age, first class medical certificates expire on the last day of the month they were issued, one year from the date of issue. The FAA introduced this rule on July 24, 2008.[34][35]
For all others, they are valid until the last day of the month, six months after they were issued. The certificate holder may then only exercise the privileges of a second class medical certificate until the last day of the month, twelve months after the certificate was issued, thereafter the privileges of a third class medical until the last day of the month, twenty four months after the medical was issued ( FAA $61.23 (d-1-iii) ).
Special issuance
Pilots who do not meet the above requirements may be issued a medical certificate under a "special issuance." A special issuance is essentially a waiver for a disqualifying condition and are evaluated case-by-case depending on the class of certificate requested. Minor problems can be overcome by a special issuance from an Aviation Medical Examiner, while others require a special issuance from the FAA directly.
Restrictions
Restrictions may be placed upon a medical certificate to mitigate any concern for safety. A common restriction for pilots who require glasses or contacts to meet the required visual acuity standards is that they "MUST WEAR CORRECTIVE LENSES."  Color-blind pilots are typically issued a restriction reading, "NOT VALID FOR NIGHT FLIGHT OR BY COLOR SIGNAL CONTROL."  This mitigates the concern that color-blind pilots may not be able to identify those colors required for the performance of safe airman duties by preventing situations that are considered potentially unsafe.
For color vision deficient pilots, in many cases these restrictions can be removed through use of an FAA approved alternative office based color vision test, which if passed, the applicant must continue to retake that same test (or any other passable tests) at every renewal.  If the pilot applicant is unable to pass any of the office based tests, a real world operational test is available.  This test consists of a ground-based chart reading and control tower signal light test for Third Class medical certification (This is called the Operational Color Vision Test or OCVT), and in addition to that, a specialized "Medical Flight Test" (MFT) is required for Second and First Class medical certification.  The applicant performs an actual flight test with an FAA Aviation Safety Inspector (ASI) for the purpose of further demonstrating "the ability to perceive those colors necessary for the safe performance of airman duties", which is the color vision requirement as written in the FARs.  Note that "Normal Color Vision" is not required, as a certain amount of color vision deficiency is considered safe and permitted.  If the tests are passed, a "Letter of Evidence" (LOE) from the FAA is issued, which serves as evidence that the pilot meets the standards for Color Vision and the AME is permitted to issue the class of Medical Certificate indicated on the LOE (All classes if both the OCVT and MFT are passed) with no related restriction if all other medical requirements are met.  This allows the pilot to receive a medical certificate with no restrictions related to color vision without the requirement of passing an office based color vision test at every subsequent renewal.[38]
Non-pilot certifications
In addition to pilot licenses the FAA also issues other airmen certificates.
Flight Instructor certification is separate from pilot certification.  For every rating on a flight instructor certificate, there must already be a corresponding rating on the individual's commercial pilot certificate.  The applicant must also pass written and flight skills tests.
Flight Engineer Certifications are applicable to large transportation aircraft (more than 80,000lb). Flight Engineer Certificates are further Rated by type of engine they are trained and tested on: Turbojet Powered, Turbopropeller Powered, Reciprocating Engine Powered. Flight Engineers are becoming less common as modern jets move towards two person flight crews.
Flight Navigators certificates are still available, but modern technology and the high speed of jets has made the rating obsolete.
Aviation Medical Examiner, Ground Instructor, Parachute rigger, Aircraft Maintenance Technician, Repairman and Air Traffic Controller are also federally certificated aviation-related positions.  Most of these also have their rating systems.  For example, an A&P is a certificated mechanic with both airframe and powerplant ratings, and a Ground Instructor may be rated to give Basic, Advanced, and/or Instrument training.  Aircraft Inspection authorization (IA) is an additional privilege conferred on certificated mechanics who meet specific experience and training requirements.
An Aircraft Dispatcher Certificate is required for people involved in operational control/dispatch under 14 CFR Part 121 commercial operations. Qualification requirements can be found in
Pilots do not need FCC licenses to use the radio within the United States (pilot certificates double as FCC radio licenses); however, other countries may require that a pilot have an FCC Restricted Radiotelephone Operator Permit (RR), and the aircraft radio station be licensed.
Flight attendants are trained to the level required to earn an FAA Certificate of Demonstrated Proficiency.  This is not considered to be an airman certification.
Avionics Techs. General radiotelephone operator license or (GROL) are certificated by the FCC.
Costs and Ways to Save Money
Each certification varies in cost and depends on aircraft rental and instructor rates at a given flight school. On average, these are the costs[39] for each pilot certification from least to greatest:
Sport – $4,400
Recreational – $7,700
Private – $9,900
Commercial (includes Complex/High Performance Training) – $4,000[40] to $8,500[41]
Other ratings:
Instrument (IFR) – $3,000[42] to $7,500[43]
Multi-Engine – $800[42] to $5,000[40]
Becoming a pilot is expensive but there are many ways to save money:
Seek internships or small jobs at flight schools or airports
Prepare and study hard for tests and check-rides to complete stages faster (saving money)
Buddy-up or share flights with other pilots while training or building hours. Join pilot clubs to meet other pilots or use smart phone apps such as BuddyFlight for connecting with other pilots[44]
Use a simulator whenever possible
Apply for scholarships
Choose a flight school with a good reputation[45]
Join the Civil Air Patrol (CAP)
Build good credit (to get good rates on loans)
Get your CFI certificate and instruct other pilots while gaining hours at no cost
See also
Alien Flight Student Program
Civil Aerospace Medical Institute
Glider pilot license
Paragliding
Ultralight aviation

 — pilot certification regulations can be found at Parts 61 and 141.

How long does it take to get private pilots license in USA?


Leucine rich repeat and Immunoglobin-like domain-containing protein 1[1] also known as LINGO-1 is a protein which is encoded by the LINGO1 gene in humans.[2][3] It belongs to the family of leucine-rich repeat proteins which are known for playing key roles[4] in the biology of the central nervous system. LINGO-1 is a functional component of the Nogo (neurite outgrowth inhibitor) receptor also known as the reticulon 4 receptor.
It has been found that LINGO-1 antagonists such as BIIB033[5] could significantly improve and regulate survival after neural injury caused by the protein.[6]
Structure

The human LINGO-1 is a single-pass type 1 transmembrane protein of 614 amino acids. It contains a signal sequence of 34 residues, followed by a LRR (leucine-rich repeat) domain, an Ig (immunoglobulin-like) domain, a stalk domain, a transmembrane region and a short cytoplasmic tail. As a transmembrane protein, it can mostly be found on the cell membrane.[7]
The LINGO-1 structure has been shown to be highly stable both in its crystal form and in solution, thanks to its leucine-rich repeat Ig-composite fold. Since the tetramer has a very large surface area into the cell membrane, it is thought that this may serve as an efficient and stable binding platform, facilitating the interaction with NgR, p75, TROY complex.

Extracellular domain
The extracellular domain consists of the signal sequence, 11 LRR motifs comprised between an N-terminal and  C-terminal capping domains, and the Immunoglobulin-like (IgC2) domain.[3][8] The C-terminal LRR domain is essential for the protein's function with its screening for proteins that interact with this domain. The structure, together with biophysical analysis of LINGO-1 properties have revealed that the protein's LRR-Ig composite fold of the protein can drive it to associate with itself in a circular ring-like form, creating a closed and stable tetramer in solution and in crystal.
Intracellular domain
The intracellular part of the protein is formed by the transmembrane region and a cytoplasmic tail of 38 residues. It contains a canonical Epidermal Growth Factor Receptor (EGFR)-like tyrosine phosphorylation site on the 591 residue that is critical for intracellular signals.[9]
Co-receptor
LINGO-1 is a co-receptor that interacts with the ligand-binding Nogo-66 receptor (NogoR) in the Nogo receptor signaling complex.[8] The Nogo receptor complex is formed when Nogo-66 binds to its receptor.[10]
LINGO-1 is an homotetramer which forms a ternary complex with RTN4R/NGFR and RTN4R/TNFRSF19.
Post-translational modifications
LINGO-1 contains several N-glycosylation sites that could have a negative effect on its capacity to self-interact with cis or trans, with other partners, or gangliosides.[11] It also contains high-mannose glycans.
Tissue distribution

LINGO-1 is expressed almost exclusively in the central nervous system (CNS). It can be found in the brain and in neurons and oligodendrocytes. LINGO-1 mRNA is expressed in an almost exclusive manner in the central nervous system during both embryonic and postnatal stages. It is targeted to the plasma membrane of neurons, but it is possible that a smaller quantities of the protein may be found in other intracellular compartments.[12] Its highest expression is in specific adult human brain regions such as the cerebral cortex, a region involved in sensory-motor function, cognition and working memory; the hippocampus, responsible for long term memory and the encoding and retrieval of multi-sensory information; the amygdala, implicated in the stress response; as well as the thalamus, with a more constant and basal level of expression across the remainder of the brain.[13]
Function and mode of action
Since LINGO-1 is a leucine-rich repeat protein, which are known for their important role in protein-protein interactions in a wide variety of cellular processes and their implication in important functions like neuronal differentiation and growth or the regulation of axon guidance and regeneration processes, it is logical to deduce that its functions are linked with the nervous system.
LINGO-1 is an essential negative regulator of myelination. It has been implicated in the inhibition of axon regeneration through a ternary complex formed with NgR1/Nogo-66 (ligand-binding subunit) and p75 (signal transducing subunit). NgR1 relies on its co-receptors for transmembrane signalling.The three major myelin-associated inhibitory factors are Nogo, oligodendrocyte myelin glycoprotein, and myelin-associated glycoprotein which all share this trimolecular receptor complex. The inhibitory action is achieved through RhoA-GTP upregulation in response to the presence of MOG, MAG or Nogo-66 in the central nervous system.[8]  LINGO-1 also inhibits oligodendrocyte precursor differentiation and myelination, by a mechanism that also involves activation of RhoA, but which apparently does not require p75 or NgR1.
LINGO-1 is involved in the regulation of neural apoptosis by inhibiting WNK3 kinase activity. It has been shown that blocking the extracellular domain of LINGO-1 disrupts the interaction between receptor kinases and LINGO-1 which directly attenuates inhibition of neuronal survival. However among the four WNK family members, only WNK3 has been shown to regulate and increase cell survival in a caspase-3-dependant pathway.[11][14]
To be able to understand how these components regulate signalling processes an experiment has been set up "model of serum deprivation" (SD) to prompt neuronal apoptosis. Research shows that treatments either with a construct containing the IgC2 or EGFR domains in the LINGO1 protein or with Nogo66 which act like a NgR1 agonist, therefore initiating a physiological response when combined with the receptor, resulting in an increased rate of apoptosis in primary cultured cortical neurons under SD.
In addition, reducing the expression levels of the serine/threonine Kinase WNK3 (using gene silencing via RNA interference (ShRNA)) or inhibiting its kinase activity had similar effects on the survival of such neurons. The adverse effects of Nogo66[15] have proved to enhance the co-association of LINGO1 and WNK3, causing the binding of WNK3 to the intracellular domain of LINGO1 leading to reduced WNK3 kinase activity. LINGO1 promotes neural apoptosis by inhibiting WNK3 kinase activity.[16]
Signaling pathways
LINGO-1 is able to interact with different co-factors and co-receptors, which can lead to the activation o signaling pathways that can have an effect on the regulation of neuronal survival, axon regeneration, oligodendrocyte differentiation, or myelination processes in the brain.[17]
Known interactions are with proteins such as Oligodendrocyte-myelinn glycoprotein, Nogo-A (neurotic outgrowth inhibitor), and myelin associated glycoproteins. LINGO-1 also interacts with transmembrane proteins: EFGR, along with its ligand epidermal growth factor (EFG); brain derived neurotrophic factor (BNDF) and its receptor, amyloid precursor protein (APP), and tropomyosin receptor kinase A (TrkA). There are other interactions with proteins that are implicated in neurological and psychiatric disorders: WNK lysine deficient protein in kinase 1 (WNK1), mitogen activated protein kinase 2/3 (MEK 2/3), extracellular signal reduced kinase 5 (ERK5), RhoA, and others.[18]
Neurological and psychiatric disorders

LINGO-1 is coded by the LINGO-1 gene, which is located on the human chromosome 15, more precisely on the locus 15q24-26, which is a region that has a primordial implication in number of psychiatric, addictive and anxiety related disorders. Genomic alterations of this regions can be factors for disorders such as schizophrenia, depression, autism, panic disorder or anxiety.[19]
Brain regions identified as highly expressing Lingo-1 transcripts have also been heavily implicated in both neurological and psychiatric disorders such as spinal cord injury, traumatic brain injury, multiple sclerosis (MS), Parkinson’s disease, essential tremor (ET), Alzheimer’s disease, epilepsy and glaucoma (central nervous system diseases); as well as stress and panic disorders, schizophrenia, amnesia, etc.[13] The role of Lingo-1 in these neurological disorders consists on its inhibitory role in neurite outgrowth, oligodendrocyte differentiation and myelination, making it difficult for the nervous system to regenerate the injured areas, whether these injuries come from endogenous or exogenous processes.
Spinal cord injury
Spinal cord injury results in the damage of the axonal tracts whose function is to control motor and sensory activity. This protein has been found in this axonal tracts of adolescent rat spinal cords following injury. Furthermore, a five time increase in Lingo-1 mRNA levels was detected 14 days post injury. Lingo-1-Fc, a soluble form of Lingo-1, has also been shown to antagonize Lingo-1 signaling pathways by inhibiting the binding of Lingo-1 to NgR, in consequence, vast improvements in the functional recovery of rats following lateral hemisection of the spinal cord were observed.[13]
Essential tremor and Parkinson
Essential tremor, one of the most common neurological diseases, is characterized by postural and action tremor. Recent research shows that around the 20% of people who suffer this disease have an increase of the protein LINGO1 in their cerebellum, therefore linking LINGO1 to essential tremor would result in the development of more effective symptomatic therapies and treatment.[20][21][22]
It has been found that there is a marker in LINGO-1 genome, a variant (rs9652490) that is significantly associated with essential tremor, increasing the risk of having the pathology.
As for Parkinson's disease, which is also an age-related movement disorder, it was discovers that levels of LINGO-1 are more elevated in the substantia nigra of post-mortem Parkinson's disease brains compared to control groups. It is thought that dopamine neuron survival and behavioral abnormalities are due to the over expression of LINGO-1 in Parkinson's patients.[13]
Traumatic brain injury
Traumatic brain injury involves the necrotic and apoptotic death of brain cells in vulnerable and delicate areas such as the cerebral cortex and hippocampus, where it is known that there is an expression of Lingo-1 in both development and the adult stage of life. RhoA signaling is largely responsible for the neuronal response to neuronal inhibitory proteins and the regeneration (or lack of in case of its activation) of damaged axons. Receptor Lingo-1 stimulates RhoA, which activates ROCK (RhoA kinase) which, in turn, stimulates LIM kinase, which then stimulates cofilin, which effectively reorganizes the actin cytoskeleton of the cell. In the case of neurons, activation of this pathway results in growth cone collapse, therefore inhibits the growth and repair of neural pathways and axons. Inhibition of this pathway by its various components usually results in some level of improved re-myelination.[23] The use of Lingo-1-Fc as an antagonist for Lingo-1 shows the inhibition of RhoA activation. Since this soluble form of Lingo-1 is able to block the interactions between Lingo-1 and NgR, it is reasonable to think that the blockade of RhoA occurs at the level of Lingo-1/NgR/p75 or TROY complex, leading to the conclusion that Lingo-1plays a very important part in the lack of re-myelination, repair of neural and axon injuries, etc.[13]
Schizophrenia
Schizophrenia is a chronic, severe and disabling brain disorder.
As said before, leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) is an essential negative regulator of myelination and neurite extension. Both myelination and neurite outgrowth occur during brain maturation, and it is during this late period of brain development (adolescence and early adulthood) when schizophrenia is first expressed. In fact, myelination peaks during late adolescence, coinciding with the onset of schizophrenia. Consequently, an excessive action of Lingo-1 through demyelination and blocking neurite extension may be one of the possible causes of this disorder.
The brain regions which are highly disrupted in the pathophysiology of this disease are hippocampus and dorsolateral prefrontal cortex. Therefore, clinical studies have been developed in order to study these brain regions in people who suffer schizophrenia. To investigate the hypothesis that myelin fraction is lower in schizophrenia patients than in healthy subjects, a technique called magnetic resonance spectroscopy (MRS), which allows analysis of myelin, is used. This studies reported that there was in fact, a dysfunctional profile of myelination in these two areas of the brain in schizophrenia sufferers.[24]
Post-mortem studies were then realized in order to compare the levels of the protein Lingo-1 in these two brain regions (hippocampus and dorsolateral prefrontal cortex) between schizophrenia and healthy subjects. Effectively, it was shown that the levels of Lingo-1 where significantly higher in schizophrenia than in control groups.[25]
Taking this into account, there is a clear relationship in between schizophrenia and demyelination, therefore, this disease is linked with Lingo-1 protein. Very possibly, an effective treatment of this disease would be the use of Lingo-1 antagonists, such as Anti-Lingo-1, which would offset the lack of myelin and hopefully avoid the disease. Thus, this treatment is still in ways of development and research.[26]
Multiple sclerosis
Multiple sclerosis is among the most common neurological disorders in young adults and it consists in the destructions and damage of the central nervous system (CNS) myelin due to persistent inflammation in the brain and spinal cord. This demyelination is shown to cause mitochondrial dysfunction in axons, leading to their degeneration. These damages disrupt the ability and capacity of the CNS to communicate, causing, therefore, a wide range of symptoms including physical, mental and even psychiatric ones. The best way of re-myelination is encouraging the differentiation of endogenous adult precursor cells into mature oligodendrocytes in the injured regions. These precursor cells are called oligodendrocyte precursor cells (OPCs). It is known that in early stages of MS re-myelination can be achieved successfully and efficiently whereas it cannot in late and progressive stages. Regarding Lingo-1, we know that its signaling pathway is a negative regulator of OPCs differentiation, as well as Notch's and Wnt's.
Lingo-1 antagonists are able to promote re-myelination in CNS by means of stimulating OPCs differentiation which was before blocked by this protein. This has been seen in several experiments that resulted in significant increases of oligodendrocytes differentiation by targeting Lingo-1 with its antagonists, such as the antibody Anti-LINGO-1 (BIIB033).[27]
Glaucoma
Glaucoma is a group neurodegenerative diseases characterized by features including morphological changes in the optic nerve head and therefore in the visual fields of the patients. There are two main types; open-angle and closed-angle glaucoma. The loss of RGCs (retinal ganglion cells) and their axons  results in visual field loss.Increasing evidence also supports the existence of compartmentalized degeneration in synapses. It has been shown that the first symptoms of this disease are usually ocular hypertension. Elevated IOP (intraocular pressure) has been identified as the etiology of glaucoma which causes neural RCG degeneration in the retina.[28]
LINGO1  was found to be expressed in the normal retina and was up regulated in RCGs after the induction of ocular hypertension in a rat chronic glaucoma model. Hence LINGO1 functions as a negative regulator of neuronal survival, axonal regeneration and oligodendrocyte differentiation. LINGO1 binds with TrkA and inhibits myelination by oligodendrocytes in vitro. Further more it binds to BDNF receptor and TrkB inhibiting the activation of TkrB by binding of BNDF after the induction of ocular hypertension.
Neuroprotection of RCGs
Even though BDNF is an important survival factor for RGCs both during development and adult life,  BDNF can only slightly increase the survival rate of RCGs,[28] and does not significantly “rescue” injured RCGs in hypertensive eyes after episcleral vein cauterization. The negative regulatory function of LINGO1 may be involved in the limited neuroprotective effect of BDNF and it could be reversed after blocking LINGO1 function.
LINGO 1 negatively regulates TrkB activation through the signalling pathway of BDNF/TrKB, and anti-LINGO-1 exerts neuroprotective effects via activation of BDNF/TrkB.[29][30]
Better than BDNF and BII003 (LINGO1 antagonist) alone, the combined treatment of both provides long term RCG neuroprotection after the induction of ocular hypertension. In conclusion BII033 may provide an attractive therapeutic strategy to promote neuroprotection in glaucoma.[28]
Antagonists
Blocking the activity of lingo-1 has several potential applications in the treatment of neurodegenerative diseases.[18][31]
(A myelin sheath is a lipid protective coating that covers and protects nerve cells (axons). These sheaths makes possible rapid and accurate transmission of nerve signals. Multiple sclerosis destroys these myelin sheaths, leading to a deterioration in nerve signal transmission. Once this protective myelin coating is stripped away, it leads to apoptosis of the neuron; axons gradually die, causing the muscle spasms and paralysis that are characteristic of the disease.[32])
Anti-lingo-1 (BIIB033)
Anti-lingo-1 (BIIB033) is a monoclonal antibody specific to the lingo-1 protein and is designed to promote remyelination (the formation of new myelin on axons) and neuroprotection.[16][33]  The protein lingo-1 inhibits the action of myelin-making cells, oligodendrocytes, which are surrounding the axons. Its antagonist, the antibody anti-lingo-1  would block this protein and even would be capable of myelin repair.
A number of clinical trials of the anti-lingo-1 antibody drug (BIIB033) have either been completed or are underway.[34] Acute optic neuritis (AON) is a disease which involves damage within the nerve fibers and loss of myelin within the optic nerve (it normally involves one eye and it's characterized by inflammation).[35] One clinical trial studying the effects on BIIB033 on acute optic neuritis.[36] Throughout the study, optic nerve conduction latency was measured (the time for a signal to travel from the retina to the brain's visual cortex).[37] As about half of patients with optic neuritis will later develop multiple sclerosis, BIIB033 antibody treatment is also being considered for the former disease. It is thought that Anti-Lingo-1 would produce the necessary myelin to avoid neurodegeneration.[38]

Further reading

When was the LINGO-1 protein first identified?


Transoxiana (also spelled Transoxania), known in Arabic sources as Mā warāʼ an-Nahr (Arabic: ما وراء النهر Arabic pronunciation:[ˈmaː waˈraːʔ anˈnahr] – 'what [is] beyond the [Oxus] river') and in Persian as Farārūd (Persian: فرارود, Persian pronunciation:[fæɾɒːɾuːd]—'beyond the [Amudarya] river'), is the ancient name used for the portion of Central Asia corresponding approximately with modern-day Uzbekistan, Tajikistan, southern Kyrgyzstan, and southwest Kazakhstan. Geographically, it is the region between the Amu Darya (Ancient Greek: Ώξος Ốxos) and Syr Darya rivers.[1] The area had been known to the ancient Iranians as Turan, a term used in the Persian national epic Shahnameh,[2] and to the Romans as Transoxania (Land beyond the Oxus). The Arabic term Mā warāʼ an-Nahr (Land Beyond the River) passed into Persian literary usage and stayed on until post-Mongol times.[3]
The region was one of the satrapies (provinces ) of the Achaemenid dynasty of Persia under the name Sogdiana. It was defined within the classical world of Iran to distinguish it from Iran proper, especially its northeastern province of Khorasan[4]—a term originating with the Sasanians,[5]—although early Arab historians and geographers tended to subsume the region within the loosely defined term "Khorasan" designating a much larger territory.[6][7]
History

The name Transoxiana stuck in Western consciousness because of the exploits of Alexander the Great, who extended Greek culture into the region with his invasion in the 4th century BC; Transoxiana was the most north-eastern point of the Hellenistic culture until the Arab invasion. During the Sassanid Empire, it was often called Sogdiana, a provincial name taken from the Achaemenid Empire, and used to distinguish it from nearby Bactria.
The Chinese explorer Zhang Qian, who visited the neighbouring countries of Bactria and Parthia along with Transoxiana in 126 BC, made the first known Chinese report on this region. Zhang Qian clearly identifies Parthia as an advanced urban civilisation that farmed grain and grapes, made silver coins and leather goods.[8] It was ruled successively by Seleucids, the Greco-Bactrian Kingdom, the Parthian Empire and the Kushan Empire before Sassanid rule.
In Sassanid times, the region became a major cultural center due to the wealth derived from the Northern Silk Road. Sassanid rule was interrupted by the Hephthalite invasion at the end of the 5th century and didn't return to the Sassanids until 565. Many Persian nobles and landlords escaped to this region after the Muslim invasion. Before the Muslim invasion it was also ruled by Göktürks. After that it was ruled by Tang China until the Arab conquest between 705 and 715, the area became known as Mā warāʼ al-Nahr (Arabic, 'what is beyond the river'), sometimes rendered as "Mavarannahr".
Transoxiana's major cities and cultural centers are Samarkand and Bukhara. Both are in the southern portion of Transoxiana (though still to the north of the Amu Darya itself, on the river Zeravshan), and the majority of the region was dry but fertile plains. Both cities remained centres of Persian culture and civilisation after the Islamic conquest of Iran, and played a crucial role in the revival of Persian culture with establishment of the Samanid dynasty.
Part of this region was conquered by Qutayba ibn Muslim between 706 and 715 and loosely held by the Umayyads from 715 to 738. The conquest was consolidated by Nasr ibn Sayyar between 738 and 740, and continued under the control of the Umayyads until 750, when it was replaced by the Abbasids. The Tang dynasty also controlled the eastern part of the region until about the same time, when a civil war known as the An Lushan Rebellion occurred.
Genghis Khan, founder of the Mongol Empire, invaded Transoxiana in 1219 during his conquest of Khwarezm. Before his death in 1227, he assigned the lands of Western Central Asia to his second son Chagatai, and this region became known as the Chagatai Khanate. In 1369, Timur, of the Barlas tribe, became the effective ruler and made Samarkand the capital of his future empire. Transoxiana was known to be flourishing in the mid-14th century.[9]
See also
Sogdiana
Greater Khorasan
Khwarezm
Turan
Hisar-i Shadman