Mane Six are the group of 6 female protagonist ponies of My Little Pony: Friendship is Magic and My Little Pony: Pony Life.
The group is comprised of Twilight Sparkle (the main protagonist), Applejack, Rainbow Dash, Rarity, Fluttershy, and Pinkie Pie. Besides the Mane Six, Spike is also one of the protagonists and their good friend. Being Twilight's assistant and one of her closest childhood friends, he became a big part of the Mane 6 team later in the seasons after Season 2. Starlight Glimmer, who used to be one of their worst enemies until Twilight changed her and became one of their closest friends, is later added to the main lineup of characters from Season 6 onwards. Though she is not an official member of the Mane Six, she mostly manages to help them at some point.
The Mane Six is a fan-given name like the group does not have an official name, but the term has been adopted by the creators of the show. As of 2017, Hasbro has been using the term Mane Six in official descriptions and merchandising. It has not appeared in the show proper, however.
All of the Mane Six have been completely absent from the following episodes: On Your Marks, Hard to Say Anything, To Change a Changeling, Marks and Recreation, The Break Up Break Down, Frenemies and Student Counsel.