DYRK4

Dual-specificity tyrosine-phosphorylation-regulated kinase 4 (DYRK4), a member of the CMGC kinase family, is a serine/threonine kinase implicated in cell cycle regulation and RNA processing. Functioning through phosphorylation of substrates involved in pre-mRNA splicing (e.g., SF3B1) and chromatin remodeling, DYRK4 modulates transcriptional elongation and mitotic progression. It interacts with pathways including the Hippo-YAP/TAZ cascade, where it potentially regulates organ size and tissue homeostasis, and the mTOR signaling network through stress granule dynamics. Dysregulation of DYRK4 has been associated with renal cell carcinoma, autism spectrum disorders, and diabetes-related metabolic disturbances. While no clinical-stage inhibitors target DYRK4 specifically, preclinical studies explore ATP-competitive small molecules (e.g., harmine derivatives) for oncological and neurological applications. Structural studies reveal its unique kinase domain architecture with a conserved "DYRK-specific insert," distinguishing it from other DYRK isoforms.