Arquette, a transgender actress, died surrounded by family, her siblings Patricia, David, Rosanna and Richmond confirmed. Her cause of death was unspecified, reported People.
"Our sister, Alexis Arquette, passed away this morning, September 11th, 2016," they said.
Arquette's brother Richmond also announced her death on a Facebook post, saying she died while listening to David Bowie's "Starman".
"Our brother Robert, who became our brother Alexis, who became our sister Alexis, who became our brother Alexis, passed this morning September 11, at 12:32 am.
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Arquette was best known for her appearances in films like "Pulp Fiction", "Bride of Chucky" and Adam Sandler comedy "The Wedding Singer".
The transgender actress was also involved in LGBT activism and documented her transition in a 2007 documentary titled "Alex Arquette: She's My Brother".
It was believed that she had been suffering from a serious long-term illness.
"RIP my sister Alexis Arquette. Another bright light gone out far too soon. Love to the family and all that loved Alexis," George tweeted.
"Friends" star Cox expressed her condolences to the family with a heartfelt message.
"My heart goes out to anyone who was lucky enough to know Alexis. We will love and miss you forever," she wrote.
Ravin posted, "Sending bunches of love to the Arquette family and friends... #RIP #AlexisArquette.
While "Sherlock" star Gatiss wrote, "I remember falling for Alexis Arquette (and Craig Chester) in a lovely and now sadly appropriately titled little film called 'Grief'."