TRAF5 (TNF receptor associated factor 5) is an adapter protein that links TNF receptor superfamily members to multiple signaling pathways, including NF-κB and JNK activation 1. As an E3 ubiquitin ligase, TRAF5 mediates protein degradation and signal transduction through its RING domain 1. Mechanistically, TRAF5 associates with receptor cytoplasmic domains and kinases to transduce inflammatory and survival signals 1. TRAF5 plays critical roles in immune regulation and disease pathology. Loss of TRAF5 expression is associated with hyperresponsive B cell activation in systemic lupus erythematosus (SLE), where TRAF5-deficient B cells exhibit enhanced TLR7 signaling and autoantibody production 2. In autoimmune diseases, TRAF5 participates in IL-17 receptor signaling complexes; SHP2-mediated displacement of TRAF5 from Act1 enables autonomous IL-17R activation that sustains inflammation despite anti-IL-17 therapy 3. TRAF5 genetic polymorphisms are associated with Behçet's disease and Vogt-Koyanagi-Harada syndrome, with functional variants regulating inflammatory cytokine production 4. TRAF5 hypermethylation reduces gene expression in ankylosing spondylitis, suggesting epigenetic regulation of autoimmune pathogenesis 5. Additionally, TRAF5 mediates AKT ubiquitination and degradation in response to nutrient signals, affecting cancer drug sensitivity 6.