Dclk1, or Doublecortin-like kinase 1, is a microtubule-associated protein kinase. It is involved in neurogenesis and has been linked to multiple important pathways like Notch, Wnt/β -catenin, and RAS, playing a significant role in various biological processes and diseases [3,4,6]. It is also recognized as a marker for certain cell types, such as tuft cells in the gastrointestinal tract and a biomarker for cancer stem cells in several cancers [3,4,5,6,7,8,9].

In atherosclerosis, macrophage-specific Dclk1 deletion in ApoE-/-mice fed a high-fat diet (HFD) attenuates the disease by reducing inflammation. Mechanistically, Dclk1 in macrophages binds to IKKβ, phosphorylates it at S177/181, activates the NF-κB signaling pathway, and induces inflammatory gene expression [1]. In obesity-induced cardiomyopathy, macrophage-specific Dclk1 knockout, rather than cardiomyocyte-specific knockout, prevents HFD-induced heart dysfunction, cardiac hypertrophy, and fibrosis. Dclk1 deficiency exerts cardioprotective effects by suppressing RIP2/TAK1 activation and inflammatory responses in macrophages [2].

In conclusion, Dclk1 plays crucial roles in inflammation-related cardiovascular diseases like atherosclerosis and obesity-induced cardiomyopathy. The use of Dclk1 knockout (KO) or conditional knockout (CKO) mouse models has been instrumental in revealing its functions in these disease conditions, highlighting Dclk1 as a potential therapeutic target for these diseases.