TRIM65, a member of the tripartite motif (TRIM) family, functions as an E3 ubiquitin ligase. It is involved in various cellular processes such as intracellular signal transduction, apoptosis, innate immunity, and carcinogenesis [1].

In terms of disease-related findings, TRIM65 deficiency alleviates renal fibrosis in mouse models induced by unilateral ureteral obstruction and folic acid, suggesting it promotes renal fibrosis through regulating NUDT21-mediated alternative polyadenylation [2]. In renal cell carcinoma, TRIM65 enhances tumor cell proliferation and acts as an oncogene via degrading BTG3 [3]. In atherosclerosis, overexpression of TRIM65 in ApoE-/-mice promotes atherosclerotic plaque development, while its genetic knockdown inhibits it, as it promotes vascular smooth muscle cell phenotypic transformation through activating the PI3K/Akt/mTOR signaling pathway [4]. In Trim65-knockout mice, isoproterenol-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction are more severe, indicating Trim65 attenuates cardiac hypertrophy by promoting autophagy and ameliorating mitochondrial dysfunction via the Jak1/Stat1 signaling pathway [5].

In conclusion, TRIM65 plays crucial roles in multiple disease conditions including renal fibrosis, renal cell carcinoma, atherosclerosis, and cardiac hypertrophy. Gene-knockout mouse models have been instrumental in revealing these functions, providing potential therapeutic targets for these diseases.