The protein expression of USP4 in liver tissue samples from patients with NAFLD was significantly lower than that of healthy controls, and mechanistically, USP4 inhibits TAK1 degradation by removing the K48-linked ubiquitinated chain, leading to inhibition of signaling activation of the downstream NF-κB and JNK cascades, which in turn reverses the disruption of IRS-AKT-GSK3β signaling, inhibits IR, and thus attenuates hepatic steatosis and inflammation (35). This evidence concerns the gene NFKB1 and metabolic dysfunction-associated steatotic liver disease.