Death-associated protein kinase 1 (DAPK1) is a serine/threonine protein kinase that plays a critical role in the pathogenesis of Alzheimer's disease (AD). DAPK1 is ubiquitously expressed in the central nervous system and its dysregulation has been implicated in various neurological diseases, including AD, ischemic stroke, and Parkinson's disease. This review summarizes current knowledge on how DAPK1 contributes to AD pathologies, including tau hyperphosphorylation, amyloid-β (Aβ) deposition, neuronal cell death, and synaptic degeneration. The molecular mechanisms underlying DAPK1 dysregulation in AD are discussed, along with recent progress in the development of DAPK1 modulators and their potential applications in AD intervention. These findings support DAPK1 as a novel therapeutic target for the development of multifunctional disease-modifying treatments for AD and other neurological disorders. DAPK1 is involved in various cellular processes, including apoptosis, autophagy, and anoikis-like cell death. It is highly expressed in the cortex and hippocampus, highlighting its role in regulating neuronal functions. DAPK1 dysregulation is associated with late-onset AD (LOAD) and is linked to genetic variations in different populations. The structural and functional properties of DAPK1 are discussed, including its kinase domain, Ca²+/calmodulin-binding domain, ankyrin repeats domain, ROC and COR domains, and death domain. These domains regulate DAPK1 activity, protein stability, and localization. DAPK1 dysregulation is observed in various neurological diseases, including AD, ischemic stroke, PD, epilepsy, and traumatic brain injury (TBI). In AD, DAPK1 expression is increased in the hippocampus and is associated with tau hyperphosphorylation. Genetic association studies have identified DAPK1 variants, such as rs4878104 and rs4877365, that may be linked to LOAD. However, the association between DAPK1 variants and AD risk is inconsistent across different populations. DAPK1 dysregulation in AD patients and mouse models is associated with increased DAPK1 protein levels, particularly in the hippocampus. DAPK1 is involved in the regulation of tau pathology through its interaction with tau proteins and phosphorylation of tau at specific sites. DAPK1 also plays a role in APP processing, Aβ secretion, and Aβ-induced neurotoxicity. DAPK1 dysregulation contributes to neuronal cell death in AD through multiple pathways, including excitotoxicity, mitochondrial dysfunction, and caspase-3-dependent apoptosis. The role of DAPK1 in AD is further supported by its involvement in the regulation of neuronal cell death, synaptic dysfunction, and neuroinflammation. DAPK1 is a promising therapeutic target for the development of disease-modDeath-associated protein kinase 1 (DAPK1) is a serine/threonine protein kinase that plays a critical role in the pathogenesis of Alzheimer's disease (AD). DAPK1 is ubiquitously expressed in the central nervous system and its dysregulation has been implicated in various neurological diseases, including AD, ischemic stroke, and Parkinson's disease. This review summarizes current knowledge on how DAPK1 contributes to AD pathologies, including tau hyperphosphorylation, amyloid-β (Aβ) deposition, neuronal cell death, and synaptic degeneration. The molecular mechanisms underlying DAPK1 dysregulation in AD are discussed, along with recent progress in the development of DAPK1 modulators and their potential applications in AD intervention. These findings support DAPK1 as a novel therapeutic target for the development of multifunctional disease-modifying treatments for AD and other neurological disorders. DAPK1 is involved in various cellular processes, including apoptosis, autophagy, and anoikis-like cell death. It is highly expressed in the cortex and hippocampus, highlighting its role in regulating neuronal functions. DAPK1 dysregulation is associated with late-onset AD (LOAD) and is linked to genetic variations in different populations. The structural and functional properties of DAPK1 are discussed, including its kinase domain, Ca²+/calmodulin-binding domain, ankyrin repeats domain, ROC and COR domains, and death domain. These domains regulate DAPK1 activity, protein stability, and localization. DAPK1 dysregulation is observed in various neurological diseases, including AD, ischemic stroke, PD, epilepsy, and traumatic brain injury (TBI). In AD, DAPK1 expression is increased in the hippocampus and is associated with tau hyperphosphorylation. Genetic association studies have identified DAPK1 variants, such as rs4878104 and rs4877365, that may be linked to LOAD. However, the association between DAPK1 variants and AD risk is inconsistent across different populations. DAPK1 dysregulation in AD patients and mouse models is associated with increased DAPK1 protein levels, particularly in the hippocampus. DAPK1 is involved in the regulation of tau pathology through its interaction with tau proteins and phosphorylation of tau at specific sites. DAPK1 also plays a role in APP processing, Aβ secretion, and Aβ-induced neurotoxicity. DAPK1 dysregulation contributes to neuronal cell death in AD through multiple pathways, including excitotoxicity, mitochondrial dysfunction, and caspase-3-dependent apoptosis. The role of DAPK1 in AD is further supported by its involvement in the regulation of neuronal cell death, synaptic dysfunction, and neuroinflammation. DAPK1 is a promising therapeutic target for the development of disease-mod