Given the strong correlation of Rhbdf2 activity with Trim31 E3 ubiquitin ligase activity, to thoroughly explore whether the Trim31–Rhbdf2 interaction significantly and positively contributes to the protective function of Trim31 on hepatic steatosis, a lentivirus loaded Trim31 with a RING-finger domain ablation (LV-Trim31 RINGΔ) was generated and used to further investigate the influence of Trim31 RINGΔ on HFD-induced liver steatosis, insulin resistance, and inflammation (Supplementary Fig. S11a and Supplementary Fig. S12a), as described in Fig. 4. Here, RHBDF2 is linked to Insulin resistance.