The Vav family (Vav1. Vav2. Vav3) comprises guanine nucleotide exchange factors (GEFs) that activate Rho/Rac GTPases to regulate cytoskeletal dynamics, cell migration, and signaling in immune, neuronal, and cancer cells. Discovered in the 1980s-90s, Vav1 was initially linked to hematopoietic signaling due to its restricted expression in blood cells, while Vav2/Vav3 are ubiquitously expressed. Structurally, all Vav proteins contain a catalytic Dbl homology (DH) domain, a pleckstrin homology (PH) domain, calponin homology (CalB) regions, and SH2/SH3 adaptor motifs enabling interactions with phosphorylated tyrosine kinases (e.g., Syk, Src) and scaffold proteins. Activation requires phosphorylation of critical tyrosine residues (e.g., Tyr174 in Vav1) within an autoinhibitory N-terminal region, releasing the DH domain to catalyze GTP-loading of Rho GTPases like Rac1. Antibodies targeting Vav1/2/3 are widely used to study their expression, activation, and subcellular localization via techniques like immunoblotting, immunofluorescence, or flow cytometry. These tools have been pivotal in revealing roles in immune receptor signaling (e.g., TCR, BCR), oncogenic pathways (e.g., EGF-mediated metastasis), and neurological functions. Dysregulation of Vav proteins is implicated in lymphoma, autoimmune disorders, and neurodevelopmental defects, driving interest in therapeutic targeting. Antibody specificity remains crucial due to structural homology among isoforms and cross-reactivity risks.