DOK3 (docking protein 3) is an adaptor protein that functions as a scaffolding platform for multimolecular signaling complex assembly. Its roles are context-dependent, involving both immune regulation and disease pathogenesis. In immune signaling, DOK3 plays a positive role in interferon-β production by enabling TRAF3/TBK1 complex formation and IRF3 activation downstream of TLR3 1. However, it also negatively regulates JNK signaling in B cells through interaction with SHIP1, demonstrating pathway-specific regulatory functions. In cancer, DOK3 shows contradictory roles across tissues. In prostate cancer, DOK3 overexpression promotes proliferation and inhibits apoptosis via NF-κB pathway activation, with high expression correlating with worse prognosis 2. Similarly, elevated DOK3 in renal clear cell carcinoma associates with advanced pathological features and poor overall survival 3. Conversely, in gliomas, high DOK3 expression correlates with immunosuppressive M2 macrophage infiltration and unfavorable prognosis 4. Cross-disease analysis identified DOK3 as a therapeutic target with anti-inflammatory and antioxidative properties, reducing pro-inflammatory cytokines and oxidative stress in glioblastoma and microglia 5. In cisplatin-induced kidney injury, DOK3 deletion protects against acute kidney injury by reducing inflammation and apoptosis 6. Recent evidence suggests DOK3 phosphorylation via TREM2 signaling reduces ERK activation, attenuating neuroinflammation in depression 7. These findings establish DOK3 as a multi-functional adaptor with context-dependent roles in immunity, cancer progression, and inflammatory diseases.