DOCK5 (dedicator of cytokinesis 5) functions as an atypical guanine nucleotide exchange factor (GEF) that activates small GTPases, particularly Rac1/2, by facilitating GDP-GTP exchange 1. Along with DOCK1, DOCK5 mediates CRK/CRKL regulation of epithelial and endothelial cell spreading and migration on type IV collagen 2. The protein forms complexes with ELMO1 and undergoes conformational changes from closed to open states upon RhoG binding, which enhances its GEF activity and membrane association 1. DOCK5 works additively with DOCK2 in neutrophils to regulate chemotaxis, superoxide production, and extracellular trap formation through Rac activation 3. In disease contexts, DOCK5 plays protective roles in diabetic wound healing by promoting keratinocyte proliferation, migration, and adhesion 4, and protects against podocyte lipotoxicity in proteinuric kidney diseases by modulating fatty acid metabolism 5. Dysregulated DOCK5 expression is associated with acute myeloid leukemia progression 6 and osteoclastogenesis regulation 7. The protein localizes to cellular membranes and cytoplasm, where it coordinates actin cytoskeleton rearrangement and cellular motility processes.