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Panettiere appeared on Fox's Ally Mc Beal as the title character's daughter, played the daughter of a man transitioning to female in HBO Films' Normal, had a recurring guest role on Malcolm in the Middle and guest starred in Law & Order: Special Victims Unit in two different roles.
In 2004, Panettiere had her first starring role in the Disney Channel film Tiger Cruise.
She began her acting career by playing Sarah Roberts on One Life to Live (1994–97), and Lizzie Spaulding on Guiding Light (1996–2000), before starring at age 10 as Sheryl Yoast in the Disney feature film Remember the Titans.
She landed a role as Sarah Roberts on the ABC soap opera One Life to Live from 1994 to 1997, which was followed by Lizzie Spaulding on the CBS soap opera Guiding Light in 1996, and again from 1997 to 2000.
While on Guiding Light, Panettiere's character Lizzie battled leukemia.
For drawing the attention of daytime viewers to the disease, and for improving national awareness, the Leukemia & Lymphoma Society gave her its Special Recognition Award.
For her performance in Lifetime Television's 1999 TV movie If You Believe, she was nominated for the Young Artist Award for Young Actress Age Ten or Under in the category of Best Performance in a TV Movie or Pilot.Panettiere became most prominent as Claire Bennet in the NBC series Heroes, which was created by Tim Kring, as a high school cheerleader with regenerative healing powers.