Ireland have picked Paddy Jackson at fly-half ahead of Ronan O'Gara for Sunday's trip to Murrayfield to play Scotland.
Uncapped Ulsterman Jackson replaces Jonathan Sexton, who is nursing a hamstring injury, in one of Declan Kidney’s biggest calls during his five-year reign as head coach.
In another bold selection, Luke Marshall - a second Ulster three-quarter who will be making his Test debut - starts at inside centre after Gordon D'Arcy was struck down by a foot injury.
But it is the decision to select Jackson that is the biggest talking point given O'Gara's status as Ireland's most capped player with 127 appearances.
The Munster veteran, who turns 36 next month and has served as back-up at fly-half since the 2011 World Cup, was expected to be Kidney's automatic choice.
But his form this season has been poor, with his substitute appearance in the 12-6 defeat against England and his performance against Llanelli over the weekend pointing to his decline and he has been retained on the bench.
"Paddy's inclusion was a challenge given the stature of Ronan O'Gara, but I think Paddy deserves a go in this one," Kidney said.
"It was a very difficult decision to leave Ronan out, it was right up there. But that's a compliment to Paddy.
"There were always going to be five changes to the side that played against England. Luke was with us all through November and accomplished himself very well."
Keith Earls fills the left wing vacancy opened by Simon Zebo's foot problem, while the suspended Cian Healy has been replaced by Tom Court at loosehead prop.
In the last of the five changes to the side defeated by England, Donncha O'Callaghan partners Donnacha Ryan in the second row with Mike McCarthy ruled out by knee ligament damage.
Ireland know they must win in Edinburgh to preserve their fading Six Nations title hopes, but they have been decimated by injury and suspension and their campaign is in danger of imploding.
Paul O'Connell and Tommy Bowe were both ruled out of the championship before it began and Stephen Ferris' chances of participating are bleak, with the subsequent loss of D'Arcy, Healy, Zebo, McCarthy and Sexton creating their injury crisis.