Speculation about Ephron's ill health hit the Internet on Tuesday (26Jun12), with some reports suggesting she had been battling cancer, and Hollywood gossip columnist Liz Smith revealed her family members were planning her funeral.
And now, Ephron has lost her fight for life. No further details were known as WENN went to press.
Ephron, the eldest of four sisters, was born in New York City to screenwriter parents, who moved the family to Beverly Hills in California when she was four.
Despite her love of film, Ephron majored in political science at Wellesley College in Massachusetts and briefly worked as an intern in the White House during President John F. Kennedy's term in the early 1960s. She also served as a reporter at the New York Post and wrote for publications including Esquire and The New York Times Magazine.
Her film career took off in the 1980s when her second husband Carl Bernstein's affair with Margaret Jay, the daughter of British Prime Minister James Callaghan, inspired her to write the novel Heartburn, which she adapted for the big screen in 1986.
She went on to write the BAFTA-winning screenplay for beloved romantic comedy When Harry Met Sally, which became a hit film starring Meg Ryan and Billy Crystal. The film also earned Ephron Academy Award and Writers Guild of America nominations.
She made her directorial debut in 1992 with This Is My Life and reteamed with Ryan a year later for her first big success as a moviemaker, Sleepless in Seattle. Director and star worked together again in 1998 on the movie You've Got Mail.
Ephron was awarded the Women in Film Crystal Award in 1994, and branched into theatre in the 2000s - her play Imaginary Friends, which explored the rivalry between writers Lillian Hellman and Mary McCarthy, was a hit in 2002 and her co-authored production Love, Loss, and What I Wore was a sell-out in Canada, New York and California following its debut in 2008.
Ephron's film projects in more recent years have included 2005's Bewitched and Julie & Julia in 2009.
She is survived by her third husband, screenwriter Nicholas Pileggi, who she married in 1987, and sons Jacob and Max.