Patients with NAFLD who carry the PNPLA3 rs738409 C/G mutation, a genetic polymorphism characterized by the substitution of isoleucine to methionine at position 148 (I148M), are more likely to develop steatohepatitis and fibrosis (16), and this nonsynonymous variant is the main genetic risk factor for disease severity and progression (Figure 3) (120, 121). The gene discussed is PNPLA3; the disease is metabolic dysfunction-associated steatotic liver disease.