In addition to targeting PNPLA3 gene variants, liver-specific acetyl-CoA carboxylase (ACC) inhibitors (MK4074) block enhanced fatty acid synthesis, improve fatty acid beta-oxidation, and then reverse the NAFLD phenotype caused by TM6SF2 defects (Li et al., 2022). Here, PNPLA3 is linked to metabolic dysfunction-associated steatotic liver disease.