DSTYK (dual serine/threonine and tyrosine protein kinase) is a multifunctional kinase with roles in cell signaling, innate immunity, and developmental processes. Functionally, DSTYK acts as a positive regulator of ERK phosphorylation downstream of fibroblast growth factor receptor activation 12 and directly phosphorylates STING at late endosomes to promote innate immune signaling against DNA viruses 3. DSTYK also phosphorylates β-catenin to suppress Wnt/β-catenin signaling and glycolytic metabolism in lung cancer cells 4. Mechanistically, DSTYK regulates lysosome biogenesis through the mTORC1/TFEB pathway, critical for notochord development and vertebral morphogenesis 5. DSTYK loss-of-function variants cause congenital anomalies of the kidney and urinary tract (CAKUT) with approximately 20-43% penetrance depending on genetic background 6 and congenital scoliosis through disrupted vertebral development 7. Clinically, DSTYK amplification in non-small cell lung cancer correlates with resistance to taxane-based chemotherapy and reduced immunotherapy response 89, suggesting DSTYK inhibition may sensitize tumors to treatment. Additionally, DSTYK variants were identified as potential causal factors in prostatitis through Mendelian randomization analysis 10.