ARHGEF6 encodes a Rho family guanine nucleotide exchange factor that specifically activates RAC1 and CDC42 GTPases 12. The protein contains conserved structural domains including an N-terminal calponin homology (CH) domain, SH3 domain, and tandem DH and PH domains 3. ARHGEF6 functions in integrin-mediated signaling by interacting with beta-parvin (PARVB) and localizing to lamellipodia and cell ruffles, where it promotes cell spreading and lamellipodia formation 41. In the inner ear, ARHGEF6 is essential for hair cell stereocilia maintenance, with knockout mice showing progressive hair cell loss and hearing loss due to decreased active CDC42 and RAC1 levels 2. Pathogenic variants in ARHGEF6 cause X-linked intellectual disability and congenital anomalies of the kidneys and urinary tract (CAKUT) through disruption of integrin-parvin-RAC1/CDC42 signaling pathways 1. The gene shows ubiquitous expression with strong early embryonic expression 3. In lung adenocarcinoma, ARHGEF6 functions as a tumor suppressor, with downregulation associated with poor prognosis and reduced immune cell infiltration 56.