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Rajskub played the clarinet in a school band and portrayed Frenchie in the musical Grease.

The title character is a 40-year-old woman who lives at home with her parents, makes crafts, and takes her art seriously.She has an educational background as a painter, having attended the San Francisco Art Institute.Rajskub has been nominated twice for a Screen Actors Guild Award; once in 2005, and again in 2007 for Outstanding Performance by an Ensemble in a Drama Series.After being a regular guest star for two seasons, Rajskub became a main cast member in the show's fifth season.By the end of the series, she was the lead female, with top billing second only to Kiefer Sutherland.

The show, written by Rajskub with help from director/developer Amit Itelman, was inspired by Rajskub’s experiences with pregnancy, childbirth and early motherhood.