TRIM56 is an E3 ubiquitin ligase that serves as a critical regulator of innate antiviral immunity and cellular homeostasis. Functionally, TRIM56 mediates lysine-63-linked ubiquitination of STING1 and cGAS in response to double-stranded DNA, promoting their oligomerization and activation of type I interferon production 1. Additionally, TRIM56 enhances TNFα-induced NF-κB signaling through TAK1 ubiquitination and potentiates TLR3-mediated antiviral responses independently of its E3 ligase activity 1. TRIM56 acts as a viral restriction factor, directly interacting with Zika virus RNA to limit infection 1. Beyond antiviral immunity, TRIM56 exhibits pleiotropic cellular functions. It promotes white adipose tissue browning by degrading TLE3 through K48-linked ubiquitination, enhancing thermogenesis and protecting against obesity 2. However, TRIM56 demonstrates oncogenic activity in multiple cancers: in gliomas, it promotes migration and invasion via IQGAP1-CDC42 axis modulation 3; in pancreatic cancer, it drives progression through TRAF6/NF-κB activation 4; and in ovarian cancer, it facilitates NNMT stabilization promoting metastasis 5. Pathologically, TRIM56 aggravates cerebral ischemia-reperfusion injury by ubiquitinating and degrading KLF4 6, and contributes to diabetic kidney disease by modulating AMPKα ubiquitination in podocytes 7. These findings indicate TRIM56 functions as a context-dependent regulator with therapeutic implications across inflammatory, metabolic, and malignant diseases.