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). Here, PNPLA3 is linked to metabolic dysfunction-associated steatotic liver disease.