England international Jack Clifford, who captained the Under-20 side to the 2013 world title, is to retire due to a shoulder injury aged just 27, he announced on Wednesday.
The Australia-born back row forward won the last of his 10 senior caps against Italy in 2017 -- he made his debut during England's Six Nations Grand Slam campaign in 2016.
However, a dislocated shoulder he suffered in what was his 100th appearance for Harlequins last September has failed to heal entirely even after two operations.
"I am absolutely gutted to have to call time on my career at a relatively early stage," he said on the club website.
"I have been at Quins since I was 13 years old and made so many good friends here.
"I will miss this environment greatly.
"I feel proud to have reached 100 appearances for Quins and it is ironic that the injury was sustained in my 100th game!"
Paul Gustard, head of rugby at Harlequins, said he would be sorely missed.
"He was a player who had the ability to change a game with his explosive pace and offloading skills which, allied to his high work rate, meant he was an important player for us last season when he was a mainstay of the side who finished fifth," said Gustard.
"He is first and foremost a great human being.
"I have enjoyed watching him grow as a person and I continually applaud his courage and tenacity to fight back from each serious injury he endured."
Clifford is the second member of the Harlequins backrow who will be missed as former England captain Chris Robshaw leaves at the end of the season to play in the United States.