The multiple Irish champion trainer has claimed the Grade One prize in each of the last three years with Vautour, Black Hercules and Yorkhill respectively and four times overall, with Sir Des Champs successful back in 2012.
This year's team includes Al Boum Photo and Invitation Only, who were second and third behind Henry de Bromhead's Monalee in the Flogas Novice Chase at Leopardstown last month.
Mullins has hinted he could split the pair, with Al Boum Photo potentially running in the RSA Insurance Novices' Chase on Wednesday, a race De Bromhead has confirmed as the preferred target for Monalee.
Mullins and De Bromhead have also confirmed Footpad and Petit Mouchoir respectively, but that pair appear on course for a clash in Tuesday's Arkle Trophy.
More certain runners in the JLT include Nicky Henderson's Scilly Isles winner Terrefort, the Paul Nicholls-trained Modus and Finian's Oscar from Colin Tizzard's yard.
Mullins has won the first two runnings of the Trull House Stud Mares' Novices' Hurdle with Limini and Let's Dance and his red-hot favourite Laurina is one of 21 contenders for this year's renewal.
The Closutton handler has also confirmed Cut The Mustard, Pietralunga, Salsaretta, Eoline Jolie and Stormy Ireland, while the home team is headed by the Stuart Edmunds-trained Maria's Benefit.
Henderson's Thomas Campbell heads 41 horses standing the ground for the Pertemps Final. Leading hopes include Gordon Elliott's Glenloe and the Philip Hobbs-trained Louis' Vac Pouch.
Sixty five horses go forward for the Brown Advisory & Merriebelle Stable Plate. The weights are headed by Hammersly Lake and Village Vic, while the well-fancied trio of Tully East, Last Goodbye and Patricks Park all remain in the mix.
Amy Murphy is hopeful of a bold showing from Mercian Prince, who is guaranteed a place in the field as the 18th horse on the list.
She said: "He was supposed to run in the Greatwood Gold Cup at Newbury, but we lost that meeting so we will head to Cheltenham instead.
"I think he's very much a forgotten horse. He's improving all the time and he'll be even better on better ground. He has a real each-way chance."
The final race on day three of the Festival is the Fulke Walwyn Kim Muir Challenge Cup. There are 45 still in contention including Mall Dini, Squouateur and Pendra.
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