Trim31, a member of the TRIM family, functions as an E3 ubiquitin ligase. It is involved in multiple cellular signaling pathways such as the p53 tumor suppressor, mTORC1, PI3K-AKT, NF-κB and Wnt/β-catenin pathways, playing a significant role in various biological processes and disease development [1].

In disease-related functional studies, Trim31-deficient mouse models have revealed its roles. In hypertensive nephropathy, TRIM31-/-mice showed aggravated hypertension-induced renal dysfunction, fibrosis, and inflammation, indicating TRIM31's protective role by promoting MAP3K7 degradation in the TGF-β1 signaling pathway [3]. In non-alcoholic fatty liver disease, hepatocyte-specific Trim31 ablation facilitated NAFLD-associated phenotypes in mice, while its gain-of-function alleviated steatohepatitis, suggesting Trim31 as an endogenous inhibitor of Rhbdf2 in this disease [2]. In Helicobacter pylori-associated gastritis, TRIM31 downregulation was observed, and TRIM31-deficient GES-1 cells showed enhanced ROS, impaired autophagy flux, and increased NLRP3 inflammasome activation [4]. Also, Trim31-/-mice were more sensitive to Candida albicans systemic infection, with dampened SYK-mediated signaling due to lack of TRIM31-mediated SYK polyubiquitination [5]. In asthma, Trim31-/-mice had more severe airway inflammation and enhanced NLRP3 inflammasome activation after ovalbumin induction [6].

In conclusion, Trim31, as an E3 ubiquitin ligase, is crucial in multiple biological processes and disease conditions. Gene knockout mouse models have significantly contributed to understanding its role in diseases like hypertensive nephropathy, non-alcoholic fatty liver disease, Helicobacter pylori-associated gastritis, fungal infection-related immunity, and asthma, highlighting its potential as a therapeutic target.