In a recent study, we observed that protein levels of macroH2A1.2, but not macroH2A1.1, are dramatically increased in the liver of the high-fat/diethynitrosamine diet and the genetic liver-specific PTEN knock-out (KO) mice models of NAFLD [21], suggesting a differential functional role for these sister molecules in NAFLD pathogenesis. This evidence concerns the gene PTEN and metabolic dysfunction-associated steatotic liver disease.