NR2E3 and lipodystrophy: Although PNR/TRβ association was ligand dependent in yeast, PPARγ/PNR dimers formed independently of exogenous ligand, likely due to the presence of endogenous PPAR agonists in yeast.2, 25, 50 These heterodimer interactions required the integrity of the AF2 helix, and were disrupted by mutations associated with human disease, such as ESCS (PNR) or lipodystrophy (PPARγ) variants.