ARHGAP39 (also known as Vilse or PORF-2) is a Rho GTPase-activating protein that negatively regulates small GTPase signaling, primarily RhoA and Rac1 1. In the nervous system, ARHGAP39 is highly expressed in the brain and plays a pivotal role in neurodevelopment, regulating apoptosis, cell migration, neurogenesis, and dendritic spine morphology in the hippocampus and cerebellum 2. At the molecular level, ARHGAP39 functions as a major binding partner of the CNK2 scaffold, where it modulates Rac GTPase cycling to maintain the balance of active GTP-bound and inactive GDP-bound states required for proper spine formation 3. Homozygous knockout of Arhgap39 in mice is embryonic lethal, and a human homozygous missense variant (c.1301G>T) is associated with lethal cerebellar vermis hypoplasia with facial dysmorphology and visual impairment 4, representing the first documented human ARHGAP39-related disorder. Beyond neurodevelopment, ARHGAP39 is widely distributed throughout the body and is aberrantly overexpressed in hepatocellular carcinoma and breast cancer, where elevated levels correlate with poor prognosis and altered immune infiltration patterns 56. ARHGAP39 is also expressed in the testis with developmental and hormonal regulation 7.