Recently Lindén et al. demonstrated that silencing PNPLA3 in hepatocytes ameliorates NASH and fibrosis in human PNPLA3 I148M knock-in mice but not wild-type mice, supporting a key role of hepatocyte PNPLA3 I148M in disease progression and as a potential target of therapeutic intervention [12]. Here, PNPLA3 is linked to metabolic dysfunction-associated steatohepatitis.