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Penny Marshall, the nasal-voiced co-star of the slapstick sitcom Laverne & Shirley and later the chronically self-deprecating director of hit films such as Big and A League of Their Own, died on Monday at her home in Los Angeles. She was 76.

Her publicist, Michelle Bega, said the cause was complications of diabetes. In recent years, Ms. Marshall said she had recovered from lung cancer, apparently discovered in 2009, and a brain tumour.

Ms. Marshall became the first woman to direct a feature film that grossed more than $100-million when she made Big (1988). That movie, a comedy about a 12-year-old boy who magically turns into an adult (Tom Hanks) and then navigates the grown-up world, was as popular with critics as with audiences.

The Washington Post said it had “the zip and exuberance of a classic romantic comedy.” The Los Angeles Times described it as “a refreshingly grown-up comedy” directed “with verve and impeccable judgment.” MT. Hanks received his first Academy Award nomination for his performance.

Four years later, she repeated her box-office success with A League of Their Own, a sentimentally spunky comedy about a wartime women’s baseball league with an ensemble cast that included Madonna, Geena Davis, Rosie O’Donnell and Mr. Hanks.

In between, she directed Awakenings (1990), a medical drama starring Robert De Niro as a patient coming out of an encephalitic trance and Robin Williams as the neurologist who helps him. Awakenings, based on a book by Oliver Sacks, was only moderately successful financially, but Mr. De Niro received an Academy Award nomination.

A writer for Cosmopolitan magazine once commented that Ms. Marshall “got into directing the ‘easy’ way – by becoming a television superstar first.” That was a reference to her seven seasons as Laverne DeFazio, the brasher (yet possibly more vulnerable) of two young roommates, brewery assembly-line workers, on the hit ABC comedy series Laverne & Shirley, set in 1950s and ‘60s Milwaukee.

In Hollywood, Ms. Marshall had a reputation for instinctive directing, which could mean endless retakes. But, she was also known for treating filmmaking as a team effort rather than a dictatorship.

That may or may not have been a function of her self-effacing personality, which colleagues and interviewers often commented on. But in 1992, Ms. Marshall confessed to The New York Times Magazine that she wasn’t completely guileless.

“I have my own way of functioning,” she said. “My personality is, I whine. It’s how I feel inside. I guess it’s how I use being female, too. I touch a lot to get my way and say, ‘Pleeease, do it over here.’ So it can be an advantage – the antidirector.”

Carole Penny Marshall was born on Oct. 15, 1942, in the Bronx, N.Y., and grew up there at the northern end of the Grand Concourse. Her father, Anthony, was an industrial filmmaker, and her mother, Marjorie (Ward) Marshall, taught dance. The family name had been changed from Masciarelli.

After she graduated from Walton High School in the Kingsbridge section of the Bronx, Ms. Marshall attended the University of New Mexico. There she met and married Michael Henry, a college football player. They had a daughter, but the marriage lasted only two years, and Ms. Marshall headed for California where her older brother Garry had become a successful comedy writer.

She made her film debut in The Savage Seven, a 1968 biker-gang drama, and had a small part the same year in How Sweet It Is!, a romantic comedy starring Debbie Reynolds and James Garner.

Ms. Marshall continued acting, mostly playing guest roles on television series, until she got her big break in 1971 when she was cast in the recurring part of Jack Klugman’s gloomy secretary, Myrna Turner, on the ABC sitcom The Odd Couple. Her brother, a producer of the show, got her the job, but nepotism had nothing to do with it when viewers fell in love with her poker-faced humour and Bronx-accented whine.

That same year, she married Rob Reiner, who was then a star of the hit series All in the Family. He adopted her daughter, but they divorced in 1979 when Laverne & Shirley and Ms. Marshall were at the height of their television popularity.

That series grew out of a 1975 episode of Happy Days, in which Laverne (Ms. Marshall) and Shirley Feeney (Cindy Williams), two fast blue-collar girls, turned up at the local hangout as blind dates for Richie Cunningham and Fonzie, the two lead characters.

When Laverne & Shirley ended in 1983 after considerable on-set conflict between the co-stars and a final season without Ms. Williams, it was the first time in 12 years that Ms. Marshall had not had at least a relatively steady job on a television series.

She began making a handful of films and television appearances. Then Whoopi Goldberg, a friend, asked her to take over for a director she wasn’t getting along with on Jumpin’ Jack Flash (1986), a comic spy caper. (Ms. Marshall had directed a few episodes of Laverne & Shirley.) The movie was far from an unqualified success, but it led to Big.

Ms. Marshall’s two films after A League of Their Own were not as well received. Renaissance Man (1994), starring Danny DeVito as an adman turned teacher of army recruits, was savaged by critics and earned only about US$24-million, considerably less than it cost to make, in the United States (in contrast, Big earned almost $115-million). The Preacher’s Wife (1996), a remake of the heartwarming 1947 fantasy romance The Bishop’s Wife, starred Denzel Washington and Whitney Houston. Critics found it likable but weak, and it brought in just under $50-million domestically.

Ms. Marshall did not direct again until 2001. Riding in Cars With Boys, a saga of teenage motherhood starring Drew Barrymore, earned mostly positive reviews but was a box-office disappointment. It was the last film Ms. Marshall directed. Her farewell to television direction was a 2011 episode of the multiple-personalities series United States of Tara.

She devoted some time to producing, recently with the 2005 movie inspired by the classic sitcom Bewitched, and took on the occasional acting job, including a 2012 guest spot on the series Portlandia and voiceover narration in the film Mother’s Day (2016), directed by her brother who died in 2016.

Her final screen appearance was on the new version of The Odd Couple, in a November, 2016, episode that was a tribute to Garry Marshall, and featured cameos by stars from his many hit series.

Information on her survivors was not immediately available.