In the current report, we revealed that Trim31 mitigates genetically and high-energy diet-triggered insulin resistance, liver steatosis, inflammation, and hepatic fibrosis by promoting degradation of Rhbdf2 by K48-linked polyubiquitination, which results in suppression of Rhbdf2-MAP3K7 signaling and downstream events. The gene discussed is RHBDF2; the disease is fatty liver disease.