DCLK1 (doublecortin-like kinase 1) is a microtubule-associated serine/threonine kinase with diverse roles beyond its initial identification in neurogenesis. Originally characterized for involvement in neuronal migration and nervous system development 1, DCLK1 functions as a calcium-signaling regulator controlling neuronal processes. In inflammatory contexts, DCLK1 promotes atherosclerosis by binding to IKKβ and phosphorylating it at residues S177/181, thereby activating NF-κB signaling and inflammatory gene expression in macrophages 2. DCLK1 also regulates invadopodia dynamics in head and neck squamous cell carcinoma through interactions with KIF16B and RAB40B, facilitating matrix metalloproteinase-9 trafficking for extracellular matrix degradation and cell invasion 3. DCLK1 is widely recognized as a cancer stem cell and tuft cell marker, with elevated expression in gastrointestinal, breast, pancreatic, hepatic, and lung cancers 45. High DCLK1 levels correlate with poor prognosis, increased metastatic capacity, and enhanced tumorigenesis through modulation of Kras, Notch, WNT/β-catenin, and NF-κB pathways 5. DCLK1 is emerging as a therapeutic target, with DCLK1 kinase inhibitors showing promise in preclinical studies 4. Additionally, DCLK1 mediates type II alveolar epithelial cell differentiation through Hippo/YAP pathway regulation in acute respiratory distress syndrome 6.