DYRK1A is a dual-specificity kinase with both serine/threonine and tyrosine phosphorylation activity that regulates multiple cellular pathways critical for neurodevelopment and mitochondrial function. It plays a central role in DNA damage response by phosphorylating RNF169 to promote homologous recombination repair, and acts as a CTD kinase that phosphorylates RNA polymerase II to regulate transcription. DYRK1A also modulates mitochondrial protein import by phosphorylating TOM70, enabling metabolic adaptation to cellular energy demands. Pathogenic loss-of-function variants in DYRK1A cause DYRK1A syndrome, characterized by global developmental delay, intellectual disability, microcephaly, growth restriction, and feeding difficulties 1. De novo disruptive mutations in DYRK1A account for approximately 1% of sporadic autism spectrum disorders, with a specific association between DYRK1A haploinsufficiency and microcephaly as a distinguishing feature 2. Additionally, DYRK1A dosage imbalance affects skeletal health in individuals with DYRK1A syndrome 3, and the gene regulates cell cycle progression through interactions with FAM53C 4. Clinically, DYRK1A inhibitors such as harmine show promise in diabetes treatment: combination therapy with harmine and the GLP1 receptor agonist exendin-4 expanded human pancreatic beta cell mass four- to sevenfold in vivo and reversed diabetes 5. DYRK1A also represents a therapeutic target for hepatocellular carcinoma, where inhibition synergizes with OXPHOS inhibitors to activate pro-death TGF-β signaling 6. PROTAC-mediated degradation of DYRK1A and DYRK1B provides enhanced suppression of downstream signaling compared to kinase inhibition 7.