Lil Bub, one of the internet's most famous cats, has died aged eight.
The cat's owner, Mike Bridavsky, announced her death to millions of followers on social media on Monday.
Lil Bub was best known for her unusual appearance - bulbous eyes and a protruding tongue. She was rescued as a feral kitten and was born with several disorders, including dwarfism.
Mr Bridavsky said she helped raise more than $700,000 (£540,000) for animal charities during her lifetime.
"Bub has made a huge difference in the world of animal welfare, and in the lives of millions of people worldwide," a post on Instagram said.
Lil Bub found online fame because of her unique appearance. Her feline dwarfism meant she stayed kitten-sized throughout her life.
She was also polydactyl, with an extra toe on each paw, and had an underdeveloped jaw and no teeth which caused her tongue to always hang out, says a BBC report.
Mr Bridavsky originally adopted Lil Bub as the "runt" of a litter of kittens found by a friend inside a tool-shed in Indiana.
In an interview, he described her "one of nature's happiest accidents" and insisted she lived a happy, healthy life despite her various health issues.
He created a Tumblr blog for the cat in 2011 and she went viral after photographs of her ended up on the front page of discussion website Reddit.
The attention led to news articles about her and invitations to appear on US television programmes.
Lil Bub went on to gain endorsement deals, merchandise lines and even her own YouTube show and documentary series.
Her owner used her fame to raise money for charity, including help for other cats with special needs through the American Society for the Prevention of Cruelty to Animals.
Before her death, Lil Bub had been suffering from a bone infection which her owner had been sharing updates about to her 2.4m Instagram followers.
Mr Bridavsky announced on Monday that she had unexpectedly died in her sleep on Sunday morning.
The owner said his cat had "spread a message of determination, positivity, and perseverance to people all over the world" during her life.
Tens of thousands of people have commented and shared the online posts announcing the cat's death.
Among those responding on Facebook - where she had more than three million followers - were people who work for animal charities which have benefited from the funds raised by Lil Bub's owner in his cat's name.
Lil Bub's death comes seven months after the death of Grumpy Cat, another feline internet legend.