PNPLA3 and metabolic dysfunction-associated steatohepatitis: The I148M mutation in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is strongly associated with hepatic steatosis, inflammation, and fibrosis.340,341 In mice fed a NASH-inducing diet, treatment with antisense oligonucleotide (ASO) directed against PNPLA3 leads to improvements in steatosis.