TRIM22 is an interferon-induced E3 ubiquitin ligase that functions as a critical regulator of innate immunity and antiviral defense 1. The protein restricts replication of multiple viruses including HIV-1, influenza A virus, Zika virus, dengue virus, and yellow fever virus through direct targeting of viral proteins for proteasomal degradation 21. Mechanistically, TRIM22 promotes K63-linked ubiquitination of MAVS to enhance RIG-I-mediated signaling and type I interferon production, while inhibiting MAVS-NLRX1 inhibitory complex assembly 3. For Zika virus, TRIM22 specifically targets NS1 and NS3 proteins for ubiquitination and degradation 2. Beyond antiviral functions, TRIM22 exhibits tumor suppressor activity across multiple cancer types. In breast cancer, it targets copper chaperone for superoxide dismutase (CCS) for K27-linked ubiquitination and degradation, thereby inhibiting STAT3 signaling and reducing proliferation and invasion 4. In osteosarcoma, TRIM22 destabilizes NRF2 independent of KEAP1, activating ROS/AMPK/mTOR/autophagy signaling pathways 5. The protein also regulates autophagosome-lysosome fusion by mediating associations between GABARAPs and PLEKHM1, independent of its E3 ligase activity 6. TRIM22 expression is upregulated by ELF3 transcription factor during RNA virus infection, creating a positive feedback loop for antiviral responses 3.