ARHGAP31 encodes a GTPase-activating protein that functions as a negative regulator of CDC42 and RAC1 small GTPases, playing critical roles in cell migration, cytoskeletal organization, and developmental processes 1. The protein is required for proper cell spreading, polarized lamellipodia formation, and regulation of actin cytoskeletal structures through its GAP activity toward CDC42 and RAC1 12. During development, ARHGAP31 expression is restricted to terminal limb buds and craniofacial processes, sites that correspond to the anatomical defects observed in associated disorders 1. Loss-of-function mutations in ARHGAP31 cause Adams-Oliver syndrome, a rare developmental disorder characterized by scalp defects (aplasia cutis congenita) and terminal transverse limb defects 13. Interestingly, pathogenic variants typically result in gain-of-function effects through premature truncation of the C-terminal auto-inhibitory domain, leading to constitutively active ARHGAP31 that disrupts normal CDC42/RAC1 signaling 14. Beyond developmental roles, ARHGAP31 functions in intestinal stem cell responses to Wnt signaling through a DLG1-ARHGAP31-CDC42 regulatory axis 5 and may be involved in cancer-associated fibroblast biology 6. The clinical spectrum of ARHGAP31 mutations extends from isolated limb defects to complete Adams-Oliver syndrome, with variable penetrance observed among carriers 3.