DOCK9 (dedicator of cytokinesis 9) is a guanine nucleotide-exchange factor (GEF) that specifically activates the small GTPase CDC42 by exchanging bound GDP for free GTP 1. The protein contains a DHR-2 catalytic domain and recognizes CDC42 through specific amino acid residues in the switch 1 and beta3-strand regions, distinguishing it from Rac-specific DOCK GEFs 1. DOCK9 is widely expressed across tissues, with two alternative N-terminal isoforms (DOCK9.1 and DOCK9.2) showing differential tissue and cell-line distribution, particularly enriched in neural tissues for DOCK9.1 2. DOCK9 has emerging clinical significance across multiple diseases. Genome-wide association studies identified DOCK9 as a susceptibility locus for irritable bowel syndrome, with shared genetic pathways linking to mood and anxiety disorders 3. In neurodevelopmental disorders, DOCK9 variants impair CDC42/RAC signaling and actin cytoskeletal organization, contributing to microcephaly and related conditions 4. In esophageal squamous cell carcinoma, reduced DOCK9 expression correlates with poor survival and influences angiogenesis and immune response, with the DOCK9/CD31 ratio serving as a potential immunotherapy response predictor 5. Additionally, DOCK9-DT lncRNA variants associate with thyroid cancer prognosis 6, while DOCK9-AS2 regulates vascular smooth muscle cell proliferation in atherosclerosis through Wnt5a stabilization 7. A keratoconus-associated DOCK9 variant causes aberrant splicing and exon skipping, disrupting functional domains 8.