DYRK1A is a dual-specificity kinase located on chromosome 21 that phosphorylates both serine/threonine and tyrosine residues with substrate preference for proline at P+1 and arginine at P-3 1. It functions as a CTD kinase regulating RNA polymerase II-mediated transcription 23 and modulates alternative splicing through phosphorylation of splice factors 4. DYRK1A plays a critical role in homologous recombination repair following DNA damage by phosphorylating RNF169 to promote TP53BP1 removal from double-strand break sites 5. The kinase exhibits pro-survival functions, negatively regulating apoptosis through SIRT1-mediated inhibition of p53 activity 4. DYRK1A gene dosage is tightly regulated—increased copy number causes congenital heart defects through impaired mitochondrial function and cardiomyocyte proliferation in Down syndrome models 6, while mutations contribute to autism spectrum disorder, particularly associated with microcephaly 7. DYRK1A inhibition shows therapeutic potential in diabetes by expanding human pancreatic β cell mass and improving glucose control 89, and in gastrointestinal dysfunction associated with autism 10. Additionally, DYRK1A inhibition modulates Wnt pathway signaling for osteoarthritis treatment 4. These findings establish DYRK1A as a dosage-sensitive kinase with pleiotropic functions across development, metabolism, and neurological disease.