DYRK1B, also known as Mirk, is a member of a conserved family of serine/threonine kinases activated by intramolecular tyrosine phosphorylation. It plays diverse roles in multiple biological processes. In skeletal muscle, it blocks cycling myoblasts in the G0 quiescent state and limits apoptosis in fusing myoblasts. It is also involved in pathways like Hedgehog signaling, which affects microtubule acetylation, and the Shh/Gli pathway during spinal cord development [3,4,5].

In mouse models, DYRK1B has been extensively studied. Cardiac-specific DYRK1B overexpression leads to cardiac dysfunction, while its deletion mitigates transverse aortic constriction-induced cardiac hypertrophy and heart failure. The mechanism involves DYRK1B binding with STAT3, increasing its phosphorylation and nuclear accumulation, and downregulating PGC-1α, thus impairing mitochondrial bioenergetics [1]. In pancreatic cancer, genetic Dyrk1b loss in mouse models shows that DYRK1B blockade promotes tumoricidal macrophage activity. It attracts tumoricidal macrophages and downregulates the phagocytosis checkpoint CD24 on cancer cells, enhancing tumour cell phagocytosis [2].

In conclusion, DYRK1B is crucial in multiple biological processes and diseases. Gene knockout models, especially in mice, have been instrumental in revealing its role in heart failure and pancreatic cancer. These studies provide new insights into potential therapeutic targets for these diseases [1,2].