It is evident that TRIM8 is able to be recruited by TRIB3 and catalyzes the polyubiquitination of HNF4α at the K48 linkage on lysine 470, whereas interfering with the TRIM8-TRIB3-HNF4α interaction may regulate lipid metabolism-related genes (FABP3, DGAT2, CYP7A1, CES1, CES2, PPARα, APOB), enhancing fatty acid oxidation, reducing lipid synthesis and accumulation, promoting cholesterol metabolism and bile acid secretion, and ultimately ameliorating hepatic lipid metabolism disorders, which could provide a new potential approach for the treatment of NAFLD or even other liver diseases (104). This evidence concerns the gene HNF4A and metabolic dysfunction-associated steatotic liver disease.