TRIM35 is an E3 ubiquitin ligase with pleiotropic functions in innate immunity, metabolism, and disease pathogenesis. In immune regulation, TRIM35 mediates K63-linked polyubiquitination of TRAF3 to promote type I interferon production via RIG-I signaling 1 and catalyzes K48-linked ubiquitination of viral proteins like influenza PB2 1. It acts as a negative regulator of TLR7/TLR9 signaling by promoting IRF7 degradation 2. TRIM35 also negatively regulates cGAS-STING signaling by deubiquitinating STING, attenuating antiviral responses 3. Additionally, TRIM35 inhibits human adenovirus replication through E1A degradation 4. In metabolic regulation, TRIM35 reduces PKM2-dependent lactate production and glucose metabolism 5, suppressing the Warburg effect in breast cancer 6. It promotes amino acid transporter SLC7A5 ubiquitination in cardiac fibroblasts, enhancing mTORC1 signaling and contributing to cardiac remodeling 7. TRIM35 also monoubiquitinates histone H2B-K120 in cardiomyocytes, promoting P53 transcriptional activity and heart failure pathogenesis 8. Clinically, low TRIM35 expression correlates with poor prognosis in breast cancer and hepatocellular carcinoma 69, while TRIM35 expression predicts favorable immunotherapy outcomes in NSCLC 10. Endothelial TRIM35 suppresses vascular calcification by inhibiting MMP10 secretion 11.