• For months, the California Democrat had faced questions about alleged memory and cognitive issues.
• In April, she was admitted to hospital after a "minor fall" at her home, the latest in a series of health concerns.
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Dianne Feinstein, the California senator who served for more than three decades and was a trailblazer for women in US politics, has died aged 90.
Feinstein was the oldest member of the US Senate and voted as recently as Thursday.
For months, the California Democrat had faced questions about alleged memory and cognitive issues.
In April, she was admitted to hospital after a "minor fall" at her home, the latest in a series of health concerns.
In a statement, Ms Feinstein's office said that she passed away at her home in Washington DC overnight.
"Senator Feinstein was a force of nature who made an incredible impact on our country and her home state," the statement added. "She left a legacy that was undeniable and extraordinary."
California Governor Gavin Newsom will now have to appoint Ms Feinstein's replacement. He had previously vowed to nominate a black woman to serve out the remainder of her term, which ends in 2025.
Born in 1933, Ms Feinstein grew up in San Francisco and graduated from Stanford University before being elected to the San Francisco County Board of Supervisors in 1969.
That election was the start of a long career in public service that saw her become San Francisco's first female mayor in 1978 and eventually led her to become a senator in 1992.
She had previously announced plans to retire at the end of next year, but resisted growing calls for her to step down.
In a statement after her death, US President Joe Biden called Ms Feinstein a "pioneering American", a "true trailblazer" and a "cherished friend".
"She's made history in so many ways, and our country will benefit from her legacy for generations," Mr Biden said.
"Often the only woman in the room, Dianne was a role model for so many Americans - a job she took seriously by mentoring countless public servants, many of whom now serve in my administration."
Earlier this year, she was absent from Capitol Hill for nearly three months following a case of shingles. She took on lighter duties upon her return and moved around the US Capitol using a wheelchair. She sometimes seemed confused during interviews, and in committee hearings or floor votes.
The BBC has reached out to Ms Feinstein's office for comment on her death.
Ms Feinstein was well known as a vocal advocate for gun control measures, and an ardent supporter of the assault weapons ban signed into law by President Bill Clinton in 1994.
Earlier in life, she became San Francisco's mayor after her predecessor, George Moscone, and city councilman Harvey Milk were shot dead.
She later recounted rushing to Mayor Moscone's office and finding a bullet wound as she searched for his pulse - an experience she said left an indelible impression on her.
As a senator, Ms Feinstein was the first woman to chair the powerful Senate Intelligence Committee, where she led a years-long review of the CIA's controversial interrogation programme of foreign terrorists in the wake of the 9/11 attacks in 2001.
"The CIA's actions are a stain on our values and our history," she said at the time, adding that "history will judge us by our commitment to a just society governed by law and a willingness to face an ugly truth and say 'never again'".
The review ultimately led to legislation barring the use of "enhanced interrogation techniques" such as waterboarding on terrorism suspects.
Ms Feinstein was also the first woman to sit on the Senate Judiciary Committee, and first female chair of the Senate Intelligence Committee.
In a 2017 interview with CNN, she said that "being a woman in our society even today is difficult".
"I know it in the political arena," she said. "We went from two women senators when I ran for office in 1992 to 24 today - and I know that number will keep climbing."
On Capitol Hill, she was known as a centrist willing to work with her Republican opponents - sometimes leading to criticism from the more left-leaning members of her own party.
News of her death quickly reverberated around the halls of power in Washington DC, with tributes pouring in from colleagues on both sides of the US political spectrum.
In a statement, California Democrat Nancy Pelosi called Ms Feinstein a "pioneering woman leader" who served with "unmatched courage, poise and grace".
"Personally, it was a great honour to serve alongside Dianne for decades - form the hilly streets of San Francisco to the hallowed halls of Congress," the statement added. "Dianne's extraordinary career will inspire countless women and girl's to pursue public service for generations to come".
Among the Republicans who have expressed their condolences is Florida senator Marco Rubio, who described her as a "political pioneer" who was "intelligent, hardworking [and] always treated everyone with courtesy [and] respect".
In recent years, worries over her declining health and cognitive abilities led some to call for her retirement and starkly highlighted concerns over America's aging politicians.
In one widely circulated video, people around her could be heard imploring her to "just say aye" during a committee vote.
She is survived by a daughter, Katherine, who reportedly has held power of attorney over her mother's legal affairs amid mounting family tensions. Her husband, investment banker Richard Blum, died last year.