TRAF4 is an adapter protein with E3 ubiquitin ligase activity that regulates diverse cellular processes through ubiquitin-mediated signaling. Functionally, TRAF4 promotes cell proliferation by facilitating EGFR dimerization and downstream AKT activation 1, and modulates osteogenic differentiation through SMURF2 ubiquitination and proteasomal degradation 2. TRAF4 catalyzes K63-linked ubiquitination of CHK1 to activate DNA repair and cell cycle arrest 3, and regulates atypical K29-linked ubiquitination of IRS1 for IGF signaling 4. Additionally, TRAF4 inhibits adipogenic differentiation by activating pyruvate kinase PKM2 and β-catenin signaling 5. Clinically, TRAF4 overexpression promotes malignant progression in multiple cancers. In glioblastoma, TRAF4 stabilizes Caveolin-1 through prevention of ZNRF1-mediated ubiquitination and facilitation of USP7-mediated deubiquitination, driving stemness and temozolomide resistance 6. In neuroblastoma, high TRAF4 expression correlates with poor prognosis and retinoic acid resistance, with TRAF4 silencing inducing apoptosis and improving treatment sensitivity 7. TRAF4 also promotes mTORC1 activation through LAMTOR1 ubiquitination, suppressing inflammation-induced colorectal cancer progression 8. In breast cancer, TRAF4 exhibits anti-apoptotic function and promotes NF-κB signaling 9. These findings establish TRAF4 as a key oncogenic regulator and potential therapeutic target across multiple malignancies.