Intriguingly, patients with NAFLD induced by a mutation in the gene encoding patatin-like phospholipase domain-containing protein 3 (PNPLA3), who are relatively protected against insulin resistance, did not show the same increase in hepatic ceramide levels, linking ceramide accumulation in NAFLD to the development of metabolic deficits [250]. This evidence concerns the gene PNPLA3 and metabolic dysfunction-associated steatotic liver disease.