DCAMKL

DCAMKL-1 (doublecortin-like kinase 1, DCLK1) is a bi-functional microtubule-associated serine/threonine kinase belonging to the doublecortin family, containing N-terminal doublecortin domains that mediate microtubule-associated functions and a C-terminal kinase domain that regulates downstream signaling processes^[1][2]. Mechanistically, DCLK1 participates in cytoskeletal regulation, cargo transport, and cellular differentiation, and has been linked to oncogenic signaling networks including Notch, Wnt/β-catenin, RAS, and epithelial-mesenchymal transition pathways^[3][4]. In disease settings, DCLK1 was initially characterized in neurodevelopment but is now widely recognized as a marker associated with tuft cells, cancer stem-like populations, tumor initiation, metastasis, therapy resistance, and tumor progression across multiple gastrointestinal and epithelial malignancies^[3][4][5]. Experimental studies further demonstrate that DCLK1-expressing cell populations contribute to stemness-associated phenotypes and pro-survival signaling, supporting its utility as a research target in cancer biology and tumor microenvironment investigations^[3][5]. Compared with related doublecortin family proteins, DCLK1 exhibits tissue-specific alternative splicing and promoter usage that generate long and short isoforms with distinct biological functions and kinase activities, a feature that complicates mechanistic interpretation and therapeutic development^[6][7]. For experimental applications, selective small-molecule inhibitors such as DCLK1-IN-1 provide valuable tools for interrogating DCLK1 kinase-dependent functions and for developing isoform-specific targeting strategies in preclinical models^[2][7].