PNPLA3 and metabolic dysfunction-associated steatohepatitis: Of note, patatin-like phospholipase domain-containing protein 3 (PNPLA3), a lipase that strongly associates with NAFLD progression to NASH and HCC [209], was also found downregulated in the liver of Hep-specific ATX deletion (ATXΔHep) mice (Figure 3B).