DOCK6 (dedicator of cytokinesis 6) is a guanine nucleotide exchange factor (GEF) that activates the small GTPases Rac1 and CDC42 1, thereby regulating Rho protein signal transduction and neurite outgrowth. In cancer biology, DOCK6 promotes aggressive phenotypes through Rac1-mediated activation of the WNT/β-catenin pathway, enhancing cancer stem cell characteristics and chemo- or radioresistance in gastric cancer 1. Similarly, DOCK6 overexpression in oral squamous cell carcinoma correlates with increased cellular migration and invasion, serving as an independent prognostic factor for poor outcomes 2. DOCK6 expression also associates with thyroid cancer prognosis as part of senescence-related biomarker signatures 3. Clinically, biallelic DOCK6 mutations cause Adams-Oliver syndrome 2 (AOS-2), a developmental disorder characterized by aplasia cutis congenita, limb defects, and neurovascular abnormalities 4. Pathogenic variants include frameshift, splice-site, and copy number alterations affecting critical DHR2 domains 4. DOCK6-related AOS shows variable expressivity, with retinal vascular pathology occurring in approximately 73% of molecularly confirmed cases 5. Recent evidence indicates biallelic DOCK6 mutations also cause familial exudative vitreoretinopathy through loss-of-function mechanisms 6. Additionally, a DOCK6 variant (p.Val45Ile) can modify the severity of Paget's disease phenotypes in digenetic inheritance with SQSTM1 mutations 7.