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Panettiere was born in and partly raised in Palisades, New York. Vogel, a former soap opera actress, and Alan Lee "Skip" Panettiere, a fire captain.
She has one younger brother, fellow actor Jansen Panettiere.
She is known for her roles as cheerleader Claire Bennet on the NBC sci-fi series Heroes (2006–10), Juliette Barnes in the ABC/CMT musical drama series Nashville (2012–present) and Kairi in the video game series Kingdom Hearts.
Other notable roles include her portrayal of the title character in the true crime drama Amanda Knox: Murder on Trial in Italy and Kirby Reed in the slasher film Scream 4.
She received two nominations for the Golden Globe Award for Best Supporting Actress – Series, Miniseries or Television Film, for her work on Nashville in 20.
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.
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.