Afeni Shakur, the former Black Panther who overcame drug addiction and inspired the work of her rap icon son Tupac Shakur before guiding his estate after his murder, has died. She was 69.

Marin County sheriff’s deputies and firefighters responded to Shakur’s houseboat in Sausalito, Calif., Monday night after she fell ill and suffered a suspected heart attack, police said.

A family member and a close friend were present when she became unresponsive, cops said.

“At this point, there is nothing to indicate to us that there was any foul play, nothing suspicious about this other than this being sadly a natural event,” Marin County Sheriff’s Lt. Doug Pittman said.

Paramedics arrived around 9:30 p.m., and Shakur was rushed to Marin General Hospital, where she was treated for about an hour before she was pronounced dead, according to Pittman.

An autopsy was scheduled for Tuesday.

“It’s a sad day,” Tupac’s biological dad, Billy Garland, told the Daily News. “Her contributions to this world will always be remembered. We weren’t really active in each other’s lives, but the pain is magnified when it’s the mother of your child.”

The New Jersey trucker, 66, recalled Shakur as a strong woman. He lamented their court battle after Tupac’s death in 1996, which ended with a judge denying his inheritance claim in 1997 because he contributed little to the superstar’s upbringing.

“We had a lot of legal issues that got blown out of proportion, and I regret that,” he told The News. “It’s just a shock that she’s gone. I hope she’ll be at peace.”

Shakur, born Alice Faye Williams in Lumberton, N.C., changed her name when she moved to New York City and joined the Black Panther movement. She and other party members were arrested in 1969 and charged with conspiracy to bomb multiple city landmarks.

In May 1971, Shakur was acquitted on all charges after she represented herself in court while heavily pregnant. She gave birth to Tupac a month later.

Shakur was the subject of her son’s 1995 hit song “Dear Mama,” which hailed her triumph over poverty and drug addiction.

“There’s no way I can pay you back/But the plan is to show you that I understand/You are appreciated,” he rapped.

After Tupac’s 1996 shooting death, Shakur took the helm of his estate, which earns more than $1 million a year. She has funneled much of the money to charity.

“She was a remarkable woman. In her youth she was a lion in the black movement. She was indefatigable,” Richard Fischbein, a New York lawyer who worked with her in the Bronx when Tupac was a young boy, told The News.

Shakur called Fischbein after Tupac’s death, and he became the administrator of the estate.

“She guided that estate in honor of Tupac. We must have put out five albums after he died. She took a lot of that money and spent her time trying to help young black kids, and kids in general,” he said.

Shakur is survived by daughter Sekyiwa Shakur, 40, who was living on a nearby houseboat. A source told The News it was Sekyiwa who called 911.

Fischbein said Sekyiwa likely will take over the estate and foundation created in Tupac’s name.

“She is going to do a great job. She’ll follow Aseni’s wishes, I’m sure,” he said.

Dina LaPolt, a California attorney who handled Tupac Shakur’s estate for nearly 10 years, fought back tears as she described Shakur, who inspired the lawyer to open up her own firm in 2001.

“She’s an advocate. She’s an activist. She taught me never to compromise your values — to always fight for what you believe in,” she told The News.

LaPolt oversaw the legal work behind 11 posthumously released albums while she represented the estate between 2001 and 2010.

The lawyer developed a close professional relationship with Shakur, who LaPolt described as “one of the smartest people I’ve ever worked with,” citing how the Black Panther represented herself in court. The activist mother also influenced LaPolt’s personal life, she said.

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Afeni Shakur, mother of hip-hop legend Tupac, dead at 69