DCLK3 (doublecortin like kinase 3) is a serine/threonine protein kinase localized to the cytoplasm and nucleus with emerging roles in neuropsychiatric and malignant diseases. The kinase exhibits distinctive autoregulatory mechanisms through autophosphorylation of its truncated C-terminal tail 1, with identified substrates including the microtubule-associated protein Tau 1. DCLK3 has been robustly implicated in bipolar disorder pathogenesis through multiple genome-wide association studies, with fine-mapping analyses prioritizing it as a likely causal gene involved in neurotransmission and neurodevelopment 23. In Huntington's disease, DCLK3 expression is markedly reduced, and its kinase activity mediates neuroprotection against mutant huntingtin toxicity through chr3 remodeling and transcriptional regulation via interaction with the SAGA histone acetyltransferase complex 4. Conversely, DCLK3 is upregulated in colon and gastric cancers, where it promotes tumor cell proliferation and inhibits ferroptotic cell death via the TCF4/c-Myc/Cyclin D1 pathway 56. Additionally, DCLK3 mediates PM2.5-induced stroke risk through altered plasma protein levels 7. These findings establish DCLK3 as a druggable kinase with therapeutic potential across neurodegenerative and malignant diseases.