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Huffman began her acting career in theatre, and in the 1990s also had many supporting roles in film and television. She starred as Dana Whitaker in the comedy-drama Sports Night from 1998 to 2000, which earned her a Golden Globe Award nomination. She is best known for her role as Lynette Scavo in the ABC comedy-drama Desperate Housewives (2004–2012), for which she earned the Primetime Emmy Award for Outstanding Lead Actress in a Comedy Series for the debut season of the series, three Screen Actors Guild Awards, and three consecutive Golden Globe nominations.

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