Hepatocyte lipid metabolism’s role as a central driver of MASLD pathogenesis is emphasized by large-scale GWAS, where the majority of genetic polymorphisms associated with the development and progression of MASLD and liver fibrosis (e.g., PNPLA3, TM6SF2, MBOAT7, and HSD17B13) (40) are genes predominantly expressed by hepatocytes in the liver that encode proteins responsible for nutrient processing, lipid handling, and the resultant hepatic mitochondrial redox state (41). Here, PNPLA3 is linked to metabolic dysfunction-associated steatotic liver disease.