The Panthers’ quest for a historic fourth consecutive NRL premiership suffered a potentially seismic blow when Nathan Cleary injured his left shoulder late in Thursday night’s 24-22 loss to Melbourne.

The talismanic co-captain appeared to twist awkwardly in a tackle with 15 minutes to play at BlueBet Stadium and was replaced by Jack Cole in the halves.

The Panthers will anxiously await the results of scans on Cleary’s shoulder before hatching a plan for the final three rounds of the regular season, and the push to a fifth-straight grand final that awaits.

Cleary is thought to have aggravated a shoulder injury that had been troubling him sporadically since the pre-season, but that he had managed to mostly overcome during his recent lay-off with a separate hamstring issue.

The halfback cut a forlorn figure in the sheds after tweaking his hamstring in the round-10 defeat of Canterbury, ultimately needing more than two months on the sidelines to recover.

Cleary’s father felt he was more upbeat after the latest setback, despite the potential ramifications for a finals campaign that is now less than a month away.

“He’s in better shape than he was when he did his hammy. Hopefully that means it’s good news,” Cleary said.

“What do you do? It’s just one of those years.”

Through five years of premiership dominance, the Panthers have become accustomed to losing Cleary for large portions of each regular season.

A long-term right shoulder injury rubbed him out on the run to the 2021 finals series and he faced a five-game ban for a horror spear tackle on Dylan Brown late in 2022.

Hamstring injuries have conspired against Cleary this season and last, but losing the representative halfback for finals would be a first for the all-conquering Panthers.

Still, Penrith have won seven of 11 games without Cleary this season, largely thanks to West Tigers-bound Jarome Luai emerging as a genuine game-manager while filling in at halfback.

“We’ve been playing games without Nathan for big chunks of the year because of his hammy,” Yeo said.

“That should give us confidence that we know we can do it. Obviously we’ll have to change a little bit but I thought ‘Romey’ (Luai) over that period of time has been really good for us.

“It just means there’s going to have to be individuals who step up. But it certainly hasn’t been new this season.”

The Panthers are likely to take a cautious approach to Cleary’s fitness given they face three bottom-eight sides to round out the regular season and are all but guaranteed a top-four finish.

The famously fastidious Cleary has been backed to again apply himself to his recovery.

“He’s the most diligent man I know, in terms of that, the confidence will be sky-high, he’ll tick every box for sure,” Yeo said.