DYRK1B is a dual-specificity kinase with both serine/threonine and tyrosine kinase activities that plays critical roles in metabolism, cancer, and development. In metabolic regulation, DYRK1B promotes hepatic gluconeogenesis by phosphorylating FOXO1 at Thr467/Ser468, enhancing its nuclear localization and inhibiting AKT-mediated phosphorylation, ultimately increasing gluconeogenic gene expression 1. DYRK1B expression is induced during fasting and in diabetic conditions, with overexpression associated with metabolic syndrome in human subjects 2. In cancer contexts, DYRK1B maintains survival of quiescent cancer cells and confers chemotherapy resistance by acting as a cell cycle checkpoint kinase 3. However, DYRK1B also has tumor-suppressive functions in pancreatic cancer, where it modulates macrophage activity and downregulates the 'don't eat me' signal CD24, promoting cancer cell phagocytosis 4. In cardiac pathophysiology, DYRK1B drives heart failure by impairing mitochondrial bioenergetics through STAT3 phosphorylation and PGC-1α downregulation 5. During development, DYRK1B regulates spinal cord ventral progenitor cells by suppressing the Shh/Gli pathway 6. These diverse functions make DYRK1B an attractive therapeutic target, with selective inhibitors showing promise in treating diabetes, cancer, and heart failure.