DAPK3 is a serine/threonine kinase functioning as a tumor suppressor with pleiotropic roles in cellular regulation. Primary function: DAPK3 regulates apoptosis, autophagy, cytoskeletal dynamics, and smooth muscle contraction through phosphorylation of multiple substrates including myosin light chains, ribosomal proteins, and kinases 1. Mechanism: DAPK3 coordinates post-translational modifications of STING to activate the cGAMP-STING-IFN-β pathway, driving anti-tumor immunity through CD8+ T cell and dendritic cell infiltration 1. In gastric cancer, DAPK3 phosphorylates ULK1 at Ser556 to activate autophagy-dependent tumor suppression 2. DAPK3 regulates actin cytoskeleton reorganization and myogenic responses in cerebral arteries independently of myosin light chain phosphorylation, likely through focal adhesion dynamics 3. In triple-negative breast cancer, DAPK3/LUZP1 heterodimers promote EMT and invasion by suppressing desmoplakin levels 4. Disease relevance: DAPK3 downregulation correlates with aggressive behavior in endometrial, gastric, and breast cancers, predicting poor prognosis 526. Metabolic regulation: insulin and glucose reciprocally alter DAPK3 DNA methylation in skeletal muscle, affecting palmitate oxidation 7. Clinical significance: DAPK3 inhibitors may provide therapeutic benefit in hypertension by reducing vascular smooth muscle contractility 8, while restoring DAPK3 activity represents a potential cancer immunotherapy strategy.