DYRK2, short for dual-specificity tyrosine phosphorylation-regulated kinase 2, is a member of the CMGC kinase family. It plays crucial roles in regulating the cell cycle, apoptosis, DNA repair, and proteostasis [1,2,3,4,5]. DYRK2 phosphorylates key substrates such as p53 at Ser46 to induce apoptosis in response to DNA damage, and is also involved in pathways like the regulation of G1/S transition, epithelial-mesenchymal-transition, and stemness in human cancer cells [3].

In hepatocellular carcinoma, liver-specific Dyrk2 conditional knockout mice and in vivo gene delivery systems revealed that Dyrk2 expression was reduced in tumours, and Dyrk2 gene transfer significantly suppressed carcinogenesis by promoting the degradation of Myc and Hras at the protein level [6]. In colorectal cancer, DYRK2 knockout decreased chemosensitivity to 5-fluorouracil and oxaliplatin in p53 wild-type cells and xenograft mouse models, while overexpression enhanced chemosensitivity through p53-Ser46 phosphorylation [7].

In conclusion, DYRK2 emerges as a key regulator in multiple biological processes, especially in cancer-related events. The use of Dyrk2 knockout and conditional knockout mouse models has significantly contributed to understanding its role in hepatocellular and colorectal cancers, highlighting its potential as a therapeutic target.