Doddie Weir has died at the age of 52, the Scottish Rugby Union has announced.
Weir was diagnosed with Motor Neurone Disease in December 2016.
The former Scotland international, who won 61 caps, used his profile to push for better research to be carried out into MND and appealed for improved care to be given to those afflicted by it.
A statement from Weir's family was published on the Scottish rugby website.
"It is with great sadness that we announce the death of our beloved husband and father, Doddie," read a statement from the family via the SRU.
"Doddie was an inspirational force of nature. His unending energy and drive, and his strength of character powered him through his rugby and business careers and, we believe, enabled him to fight the effects of MND for so many years.
"Doddie put the same energy and even more love and fun into our lives together: he was a true family man. It is difficult to put into words how much we will miss him.
"MND took so much from Doddie, but never his spirit and determination. He battled MND so bravely, and whilst his own battle may be over, his fight continues through his foundation, until a cure is found for all those with this devastating disease.
"Hamish, Angus, Ben and I would like to thank everyone for your support and for respecting our privacy at this difficult time. Kathy Weir."
A talented lock and occasional back-row, Weir played international rugby for Scotland from 1990 to 2000 and was a hugely popular member of the victorious British & Irish Lions touring squad of 1997.
Weir was a vivid presence in what was a relatively successful period for Scottish rugby, coming close to winning a Grand Slam in 1995, in which they lost the Twickenham decider to England in the final weekend.
The Scots would later win a Five Nations Championship near the close of Weir's period in the team in 1999, though the galloping lock would only feature in one game in that campaign. Legendary Scottish commentator Bill McLaren famously described his running style as akin to a "mad giraffe".
At club level, he played for the hugely successful Melrose RFC in the Borders, which dominated Scottish rugby in the early 1990s. He later transferred Newcastle Falcons, as the game turned professional, winning an English Premiership in 1997-98.
World Rugby chairman Sir Bill Beaumont paid tribute to a "remarkable man".
Beaumont said: "Today, the rugby family mourns one of its most inspirational members. His strength of character was unwavering, inspiring and moving.
"He channelled his determination into fighting his own battle, while also fighting the battle for all MND sufferers through his tireless campaigning and fundraising. Always with a smile. Quite simply, he was a remarkable man."
Scottish First Minister Nicola Sturgeon tweeted in tribute to Weir.
"This is so terribly sad. Doddie was one of our nation's sporting legends, but the brave way he responded to MND surpassed anything ever achieved on the rugby pitch.
"He refused to let it dim his spirit and did so much to help others. My condolences to his loved ones."
Irish Rugby tweeted their condolences to the Weir family on the death of a "giant of the game."
On behalf of the rugby family here in Ireland we send our condolences to the Weir family.
— Irish Rugby (@IrishRugby) November 26, 2022
Doddle was a giant of the game. A legend on and off the pitch and an inspiration to all of us.
He has left an indelible mark on the game. May he rest in peace. https://t.co/tGVngSGIoh
"On behalf of the rugby family here in Ireland we send our condolences to the Weir family. Doddle was a giant of the game.
"A legend on and off the pitch and an inspiration to all of us. He has left an indelible mark on the game. May he rest in peace."
Additional reporting: PA
