DOCK4 is a guanine nucleotide exchange factor (GEF) that activates RAC1 to regulate cytoskeletal dynamics critical for neuronal development and vascular function 1. Functionally, DOCK4 acts as an adaptor protein mediating multiple cellular processes: it promotes neurite outgrowth during neurogenesis 1, facilitates LDL transcytosis across endothelial cells by coupling SR-B1 activation with RAC1-mediated internalization 23, and mediates Nav1.7 sodium channel trafficking via interaction with the motor protein Dynein to regulate heat nociception 4. Clinically, DOCK4 loss-of-function variants cause neurodevelopmental disorder characterized by global developmental delay, microcephaly, brain malformations, hypotonia, and seizures 1. DOCK4 dysfunction also contributes to schizophrenia susceptibility, with genetic variants associated with language processing and motor coordination deficits 5. Additionally, DOCK4 hypermethylation and deletion occur in myelodysplastic syndromes, where knockdown impairs erythroid differentiation and increases apoptosis in bone marrow stem cells 6. Recent evidence links altered DOCK4 expression—regulated by histone lactylation—to abnormal pain perception in autism and other neurological conditions 4. These diverse pathogenic roles position DOCK4 as a critical regulator of neuronal and vascular homeostasis with therapeutic implications for neurodevelopmental, psychiatric, hematologic, and pain disorders.