A common polymorphism in the human PNPLA3 gene (rs738409), originating in a cytosine to guanine substitution which directs an isoleucine to methionine change at position 148 (I148M) of the PNPLA3 primary structure, is a strong genetic determinant of non-alcoholic fatty liver disease (NAFLD) and of its progression; homozygotes for the minor allele (G) present with a 10-fold risk of developing hepatocellular carcinoma compared to the other genotypes [3]. The gene discussed is PNPLA3; the disease is metabolic dysfunction-associated steatotic liver disease.