Sheila Gallagher (previously Jackson) is a former main character and agoraphobic, Frank's main love interest and a bit 'nutty' about shoes. While it's difficult for her to even think about leaving the house, she invites Frank into her home with open arms to take advantage of her cooking, disability checks and bedroom hospitality. Her clown-obsessed husband Eddie (that still resides in their basement, but then commits suicide) isn't making things any easier for her while she tries to cope with her phobias, Frank and raising their daughter Karen. According to her would be ex-husband Eddie, she takes pleasure in sexual activities and taking control, something in which Eddie found no pleasure.
Frank leaves Sheila after she begins leaving her home because he realizes she'll discover how awful he is, but a truck randomly explodes and nearly injures her undoing all Sheila's hard work in evolving.
Karen's father will her his money as atonement which irritates Frank, who attacks Jody, Karen's fiance. Seeing the real Frank, Sheila kicks him out of her home.
In Season 2 Sheila throws a party for Karen. It is noted that she is not very fond of Frank's mother, Peg. She begins to ask Frank why his mother is there, Franks tells her that his mother wouldn't miss the free food and alcohol. Sheila says that she doesn't want Peg there but Frank counters that his mother would "slaughter" him if asked to leave. Sheila goes back to the party and begins to make a speech about Karen's coming of age and all the new friends she had made, indicating Lip. Sheila also unintentionally reveals some of the unusual details of her sex life with Eddie, something that amuses Kev and Veronica greatly.
Things soon take a turn for the worse however when Sheila and Peg begin arguing. Sheila makes it clear that Peg isn't welcome as she is a convicted felon. The argument heats up and Karen and Jody are forced to come between the women and attempt to get Sheila upstairs. Kevin and Veronica are greatly amused by the whole argument and Lip begins to smirk just a little, until Peg is made so angry by a rather personal insult from Sheila that she pulls out a gun. Tony attempts to grab it from her but while everyone is panicking, a shot hits the fire detector. Frank takes this opportunity to call the police on his mother though Fiona enlists Tony's help in defusing the situation.
Sheila was getting tired from Karen's baby Hyme, whose crying constantly leads to her inviting Frank to stay since he can put the baby to sleep by slipping him a sliver of Valium.
In "Frank the Plumber", Sheila is distraught because of her daughter's continued manipulative actions that have prevented her from seeing her grandson. As a result, she doesn't speak to her and Karen is devastated at losing the one other person, besides Lip she thought she could count on. This rejection leaves her so upset that she lashes out at her mother who sits on a couch for days.
Later, Debbie visits Sheila, who confides in her about Karen, but after Debbie gives her a pep-talk that lifts her spirits, she decides to reconcile with her daughter. Sheila visits Karen and they talk about their hardships. Sheila apologizes and her attempt to reconnect nearly works as both share tears and connect again until Karen receives a text message supposedly from Lip asking to meet at the park. She is pleased to see her child happy again, with the latter telling her she really hopes to be with Lip.
Sheila gets bored with her sex life with Jody and eventually returns to Frank. A nun in a wheelchair is brought to her home by the Father, to whom the nun is taking a vow of silence. When the nun is revealed to be blogging all about Sheila's life, particularly her unorthodox sex life, Sheila smashes her iPad. Jody's sexual addiction begins to show again and around this time, she's enlisted by Frank to pose as Monica when his kids are taken away. After Karen's accident, she leaves for Arizona and Sheila is left alone. Sheila tries to cope with the fact that she's alone now and has no one after leaving Frank. Debbie shows up after Karen leaves, Sheila asks if she could help with Lip's party and Debbie agrees and allows Sheila to accompany her. Close to the Party ending Debbie sits down with Sheila and tells her that she needs to have friends in her own age group. It is possible that Sheila thinks Debbie is a replacement daughter while Karen is away. Sheila starts doing group sessions for women looking to buy sexual products.
In season 4, Sheila starts internet dating, meeting a Native American, whose 5 younger cousins she eventually wants to adopt. In order to do this, she must be married, so she tricks Frank into marrying her when he is in the hospital and thus begins calling herself Sheila Gallagher, instead of Jackson. Her request for adoption is still denied, however, and the children must live with their great-grandfather.
Just after Frank's operation, he and Sheila live together at her house. She's been caring for Frank and making sure he takes his medications. While Frank works on his "Milk of the Gods" beer in the basement, Sheila contemplates an offer made to her regarding her house: Two women would like to purchase her house for double the market value and while Sheila wants to accept and use the money to travel the world, but Frank disagrees. While the two argue over whether or not to sell, Sheila's anger toward Sammi (Frank's needy oldest daughter) grows.
Frank tries several times to convince Sheila to stay, eventually asking her to keep her house so it can be "their nest". He blames his post-transplant weakness and desire to renew his and Sheila's vows for his resistance to selling. Sheila finally decides to cancel her plans and stay with Frank, until she, Sammy, and Frank get into a fight regarding the man Frank promised sex with Sammy. Frank blows up and screams at Sammy for being needy and annoying, and proceeds to turn on Sheila and accuse her of being a "certified wack-job" and a "pervert". Then, due to Frank's beer production in the basement, Sheila's house blows up. Ignoring the flames and the burning contents of her home, Sheila walks past Frank and Sammy and into the RV she bought earlier that day. Then, she is seen driving off as Frank makes one last-ditch attempt the get Sheila to stay but she fulfills her dream of seeing the world.