TRIM4 (tripartite motif containing 4) is an E3 ubiquitin-protein ligase that plays crucial roles in innate immunity, viral defense, and cancer regulation. TRIM4 mediates K63-linked polyubiquitination of the innate immune receptor MDA5, enhancing type I interferon responses against RNA viruses 1. The protein also functions as an antiviral factor by targeting influenza A virus nucleoprotein (NP) for K48-linked polyubiquitination and proteasomal degradation, thereby inhibiting viral replication 2. In cancer contexts, TRIM4 exhibits tumor suppressor properties in breast cancer by promoting K48-linked polyubiquitination and degradation of the oncogenic protein SET, which enhances estrogen receptor-α expression and tamoxifen sensitivity 3. TRIM4 also degrades the TPL2 kinase through polyubiquitination at lysines 415 and 439, a process that is disrupted by oncogenic KRAS signaling 4. Additionally, TRIM4 mediates GAPDH ubiquitination at K254, though this is counteracted by smoking-induced succinylation 5. TRIM4 can function as a molecular glue E3 ligase, promoting neddylation-mediated degradation of CORO1A in triple-negative breast cancer 6. Pan-cancer studies have identified TRIM4 variants associated with multiple cancer types 7.