PNPLA3 and metabolic dysfunction-associated steatotic liver disease: The I148M PNPLA3 variant is a major risk factor for the development and progression of NAFLD [16-18,22,36], but the mechanism linking the 148 M allele to increased liver fat, inflammation, and fibrogenesis, and the tissue specificity of PNPLA3 physiological activity are still under definition [25,37].