DAPK1 is a Ca2+/calmodulin-dependent serine/threonine protein kinase that functions as a multifaceted regulator of cell death and metabolism. Mechanistically, DAPK1 operates through diverse signaling pathways including interactions with NR2B, p53, and Tau proteins, and its catalytic activity is inhibited by fumarate, which competes with ATP for binding 1. The kinase phosphorylates downstream targets regulating apoptotic signaling, autophagy through mTORC1 inhibition, and cellular metabolism 2. In cancer pathogenesis, DAPK1 functions as a tumor suppressor; aberrant promoter methylation silences DAPK1 expression and significantly increases gastrointestinal and cervical cancer risk (OR: 5.35-24.13) 34. In neurological contexts, DAPK1 mediates glutamate excitotoxicity-induced neuronal death via extrasynaptic NMDA receptor signaling during ischemic stroke, and contributes to Alzheimer's disease pathology through tau hyperphosphorylation and neuronal apoptosis 56. Therapeutically, DAPK1 inhibition shows promise in stroke neuroprotection and CD8+ T cell immunotherapy, while DAPK1 methylation status serves as a potential biomarker for cancer diagnosis and prognosis 71.