Kevin Sinfield is to undertake another run for Motor Neurone Disease research after raising over £2.7m by completing seven marathons in seven days in 2020.
His original run was inspired by the plight of former Leeds Rhinos team-mate Rob Burrow, who has MND.
Sinfield, 41, is now defence coach for Leicester Tigers and plans to run the 101 miles between the two stadiums.
The Extra Mile Challenge will take place on 22 November and an initial target of £100,000 has been set.
The route will be split into 7km sections and Sinfield must complete each one within 60 minutes as the next will start on the hour.
"Undoubtedly this will the toughest challenge I have ever attempted but I know it will mean so much to so many people if we can reach our fundraising target," he said.
"In my short time at the Tigers, the people in Leicester have made me feel so welcome and it is wonderful that we have been able to come up with an event that starts in Leicester and finishes with us coming home to Emerald Headingley."
In September, Burrow was among a delegation of people with MND who visited 10 Downing Street to hand in an open letter urging the government to provide £50m for targeted research over the next five years.
Sinfield led Leeds to seven Grand Final triumphs and two Challenge Cup successes during his playing career, and subsequently worked for the club in an administrative role for three years.
He moved to Leicester in the summer and has already had a major impact in helping the team win five games out of five at the start of the Premiership season.
As well as public donations, Sinfield is also hoping to enlist five benefactors willing to donate £20,000 each, which will double his initial target.
"The response from the public last year was breathtaking and I know, from feedback we have received from the MND Association, every penny that was raised has been put to good use to help members of the MND community across England and Wales," he said.
"The more money we can raise, the more people we can help and ultimately find a cure for this cruel disease.
"I am sure there will be tough times as we pound the streets during the day and night, in cold November temperatures, but knowing the good we can all achieve together will be a huge motivation for everyone involved,"