DCLK1

DCLK1, or doublecortin-like kinase 1, is a calcium/calmodulin-regulated serine/threonine kinase of the doublecortin-like kinase family. It is encoded by the DCLK1 gene and is expressed in the developing and adult nervous system as well as in select non-neural tissues. The protein contains two N-terminal doublecortin (DCX)-like domains and a C-terminal kinase domain in its long isoform; an alternative shorter isoform lacks the DCX domains while retaining the catalytic domain.

DCLK1 functions as a microtubule-associated kinase that phosphorylates substrates such as doublecortin and CRMP2, influencing microtubule stability, neuronal migration, and neurite outgrowth. In the adult intestine, DCLK1 marks a population of tuft cells and, in some contexts, quiescent epithelial stem-like cells implicated in tissue regeneration and injury responses. Through these roles, DCLK1 participates in processes of development, neurogenesis, and epithelial homeostasis.

In disease contexts, DCLK1 has attracted attention as a cancer-related marker. It is upregulated in several tumor types, including colorectal and pancreatic cancers, where it has been proposed as a marker of cancer stem cells and a contributor to tumor growth and metastasis in preclinical models. Inhibiting DCLK1 genetically or with pharmacological inhibitors often reduces tumor growth in animals, although questions about specificity and interpretation remain. DCLK1 expression levels have also been explored as potential prognostic indicators in some cancers.

Regulation of DCLK1 activity involves calcium signaling and autophosphorylation, and the protein interacts with other cytoskeletal regulators. Ongoing research continues to clarify its physiological roles and therapeutic potential, with no DCLK1-targeted therapies approved as of recent years.