Pakistan suffered a stinging setback on Monday ahead of their Test tours of Ireland and England after key leg-spinner Yasir Shah was ruled out with a hip bone injury.
The 31-year-old has been key to Pakistan's Test wins since 2014, having taken 165 wickets in 28 Test matches.
Chief selector Inzamam-ul-Haq confirmed the spinner will not be available for the tours.
"Yasir is ruled out of the Ireland and England Test tours and it's a big blow," Inzamam told local media. "It's a big loss for the team."
Medical reports said Yasir suffered a hip bone stress fracture and needs four weeks' rest in addition to another six for rehabilitation.
Inzamam said Pakistan had called on teenage leg-spinner Shadab Khan, off-spinner Bilal Asif and left-arm slow bowler Kashif Bhatti to fill in the gap.
Shadab has taken just one wicket in a single Test appearance in Barbados last year, while the others have yet to play a Test.
Yasir has taken 89 wickets in 16 of the 17 Tests Pakistan have played under head coach Mickey Arthur since May 2016.
He took a match-winning 10 wickets in Pakistan's victory at Lord's in 2016 on their way to a 2-2 series draw in England.
The leg-spinner also raced to 100 wickets in 17 Tests, while also taking 150 wickets in 27 Tests – the second-fastest player in Pakistan to achieve both milestones.
Pakistan will be Ireland's inaugural Test opponent in Dublin from May 11-15 before playing two Tests against England.
The first Test is at Lord's from May 24-28 while the second is at Leeds from June 1-5.