Rob Kearney will return at full-back for Ireland's Six Nations trip to Scotland, with Chris Farrell parachuted into the centres.
Munster powerhouse Farrell will partner Bundee Aki in midfield, with Robbie Henshaw dropping out of Ireland's match squad due to a dead leg injury.
British and Irish Lions centre Henshaw struggled positionally when shifted to full-back in last weekend's 32-20 home loss to England.
Stalwart full-back Kearney has been restored to the 15 shirt for Saturday's Murrayfield encounter then, with the 32-year-old still easing back to full sharpness after a thigh injury.
"Robbie has a dead leg and just hasn't recovered in time," said Ireland head coach Joe Schmidt.
"It's just a bit of aggravation after having a knock. It's a knock on top of a knock.
"It does make it difficult; the problem is he maybe could have played.
"But if you get another bump on it, it debilitates you quickly. And then you have to make another change."
When asked if Kearney would have returned at full-back even had Henshaw been fit, Schmidt added: "Probably once Garry Ringrose was ruled out it was going to be trying to keep a little continuity as best we can and get as cohesive as we can in a short space of time."
Potent Munster midfielder Farrell has struggled with a series of knee injuries since his last Test appearance, a man of the match showing in Ireland's 37-27 Six Nations victory over Wales in February 2018.
The 25-year-old may have just three caps to his name but Ireland rate his physical presence and capacity for industry very highly.
"You've got Chris Farrell sitting in the wings, massively motivated to do his best," said Schmidt.
"So it's a great opportunity to get him in and give him a run.
"We're just going to have to forge ahead, but it's an exciting opportunity to give Chris Farrell a run against Scotland. He's coming back to form after a long lay-off."
Connacht's Quinn Roux will replace Devin Toner to partner James Ryan at lock.
Roux failed to make the cut for Ireland's initial Six Nations squad, but has since leapfrogged provincial team-mate Ultan Dillane, who takes a seat on the bench.
Toner will miss just his seventh Test match in the Joe Schmidt era, his near-constant presence since November 2013 underscoring his importance to Ireland's line-out solidity.
Toner's ankle injury has exacerbated the absences at lock of Iain Henderson with a finger problem and Tadhg Beirne with knee trouble.
Ireland team to play Scotland
Forwards: 1 Cian Healy (Leinster), 2 Rory Best (CAPTAIN, Ulster), 3 Tadhg Furlong (Leinster), 4 James Ryan (Leinster), 5 Quinn Roux (Connacht), 6 Peter O'Mahony (Munster), 7 Sean O'Brien (Leinster), 8 Jack Conan (Leinster)
Backs: 9 Conor Murray (Munster), 10 Jonathan Sexton (Leinster), 11 Jacob Stockdale (Ulster), 12 Bundee Aki (Connacht), 13 Chris Farrell (Munster), 14 Keith Earls (Munster), 15 Rob Kearney (Leinster)
Replacements: 16 Sean Cronin (Leinster), 17 Dave Kilcoyne (Munster), 18 Andrew Porter (Leinster), 19 Ultan Dillane (Connacht), 20 Josh van der Flier (Leinster), 21 John Cooney (Ulster), 22 Joey Carbery (Clontarf), 23 Jordan Larmour (Leinster)