PNPLA3 and fatty liver disease: For instance: (1) hepatic steatosis typically starts in Zone 3 [23] in metabolic dysfunction associated fatty liver disease (MAFLD) and alcohol-related liver disease likely due to the lower metabolic activity; (2) drug-induced liver injury is most significant in the pericentral area as a result of drug catabolism; (3) disease related to impaired metabolism may manifest preferentially in Zone 1; and (4) Zone 1 predilection of pediatric NAFLD may in part be driven by genetic variants impacting lipid and lipoprotein metabolism, such as PNPLA3 [24].