It's the combination that helped spark a late charge into the Telstra Premiership finals last year and is again faced with the task of guiding Penrith into the top four with three games remaining.
Tyrone May and Nathan Cleary were household names coming through the lower-grade systems at the Panthers, winning junior titles under then-NYC coach Cameron Ciraldo.
May burst onto the scene in round 19 last year during a clash against the Warriors that ignited a season turnaround with the 22-year-old scoring five tries in nine appearances.
Along with Cleary the pair linked for four wins from seven games before May suffered an ACL injury in the semi-final loss to Brisbane at Suncorp Stadium.
The early career record gives Ciraldo, now the NRL side's caretaker coach, confidence the side can compete in their final regular season games without James Maloney.
"They both know each other's game really well, there'll be no panic between them," Ciraldo said.
"Tyrone's a five-eighth that can play lock, back-row and has played in the middle lately. He's a tough player but can defend well and will do that tomorrow. They're calm with how they want to play."
Maloney was in a knee brace on Friday following confirmation he has a grade two medial ligament sprain. The club is hopeful he will be back for week one of the Telstra Premiership finals.
Panthers v Knights - Round 23
"We spoke about resting him anyway so it was an enforced rest," Ciraldo said.
"He was probably going to be not playing this week anyway. Tyrone was going to get a shot.
"Hopefully it's a blessing in disguise but we won't know until later in the year."
Newcastle are expected to make a positional switch of their own in the playmaker role with Kalyn Ponga training alongside Mitchell Pearce in the halves throughout the week.
Bulldogs-bound fullback Nick Meaney is likely to come into fullback with Ponga in the front line.
"He's a brilliant player no matter where he plays," Ciraldo said of Ponga.
"He showed in Origin it doesn't matter which position he's in, he's a quality player and how tough it is.
"We've done a fair bit of homework on him this week but sometimes he's such a good player we want to limit his involvement.
"We've got to worry about our own attack [rather] than target anyone else but I think Kalyn has showed he's no spot player.
"There's no easy games at the back end of a year and Newcastle is a talented team. We need to build a performance that we're proud of. We need to be better."
Ciraldo confirmed James Tamou had overcome an ankle injury but said a couple of players required fitness tests on Friday.