TRAF6 (TNF receptor associated factor 6) is an E3 ubiquitin ligase that primarily catalyzes K63-linked polyubiquitin chains to regulate multiple cellular processes 1. The protein functions as a critical signaling adapter in immune and inflammatory pathways, mediating NF-κB activation through ubiquitination of key substrates including ECSIT and BECN1 1. TRAF6 plays essential roles in autophagy regulation by interacting with MAP1LC3B/LC3B and promoting selective autophagic degradation of proteins like CTNNB1/β-catenin, which suppresses epithelial-mesenchymal transition and cancer metastasis 2. In immune responses, TRAF6 promotes CTLA-4 degradation through K63-linked ubiquitination, enhancing CD8+ T-cell antitumor immunity via the OX40-TRAF6 axis 3. The protein contributes to cancer progression through multiple mechanisms, including PD-L1 upregulation via YAP1-TFCP2 signaling in melanoma 4 and metabolic reprogramming in leukemia through the TRAF6/OGT/O-GlcNAc pathway 5. TRAF6 also mediates inflammatory responses in cardiovascular disease, promoting abdominal aortic aneurysm development through macrophage pyroptosis via the NLRP3/Caspase1/GSDMD pathway 6. Its activity is negatively regulated by PRDX1, which inhibits its ubiquitin-ligase function 1.