Gloucester winger James Simpson-Daniel has been forced to retire with immediate effect because of injury.
The 32-year-old, who won 10 England caps, had been sidelined since November 2013 with an ankle problem.
Simpson-Daniel spent his entire 14-year career at Kingsholm, making more Premiership appearances for the club than any other player and scoring 118 tries in 272 games.
"I don't think it's really sunk in yet to be honest," he said.
"When I was given the diagnosis by the specialist, they were obviously the last words I wanted to hear. But I know that I've given it everything and I can't praise the Gloucester medical staff highly enough.
"I've had a really good trot, I can't have any complaints."
Simpson-Daniel joined Gloucester as a teenager and scored a try on his first-team debut against Rotherham in 2001.
He won his first England cap a year later but his international career was hindered by injury and illness, as he caught glandular fever and was hit by back, shoulder and ankle problems.
His final game for the Cherry and Whites turned out to be in their LV= Cup win over Newcastle in November, when he dislocated and fractured the joint in his left ankle.
It was his second major setback inside 12 months, having undergone a shoulder operation in November 2012 which forced him to miss the remainder of that campaign.
Despite his problems, Simpson-Daniel had been awarded a new deal to keep him at Kingsholm for the forthcoming season.
"He was a unique talent. I played against him and, even though he was an opponent who could really hurt you on the pitch, he was a joy to watch," said Gloucester's new director of rugby David Humphreys - formerly of Ulster and Ireland.
"It's a real blow for him and, personally, I'm disappointed that he's had to retire before I had the opportunity to enjoy seeing him play as a colleague."
Rugby Players' Association chief executive Damian Hopley, a former England player himself, added: "Whilst his catalogue of injuries robbed James of many more England caps, his impact for Gloucester was nothing short of sensational as he proved himself to be one of the most dangerous broken field runners the professional game has ever seen."