Our observation of an interaction between the PNPLA3 rs738409 variant and the high n-6/n-3 PUFA suggests that we could provide a targeted therapy to subjects with NAFLD homozygous for the minor allele either reducing the dietary n-6 amount or alternatively increasing dietary intake of foods rich in n-3 PUFA, such as salmon, tuna, and flaxseed oil, or supplementing the diet with n-3 PUFA. This evidence concerns the gene PNPLA3 and metabolic dysfunction-associated steatotic liver disease.