ARHGAP35 encodes p190A RhoGAP, a major tumor suppressor that functions as a GTPase-activating protein with dual roles in cytoskeletal regulation and transcriptional control 1. The protein primarily inactivates RhoA GTPases while promoting Rac activity, with this selectivity regulated by acidic phospholipid binding and PKC phosphorylation 1. ARHGAP35 activates the Hippo-YAP tumor suppressor pathway through interactions with p120 RasGAP and ZO-2, promoting contact inhibition and mesenchymal-to-epithelial transition 2. Loss-of-function mutations significantly impact human development and disease. In endometrial cancer, ARHGAP35 mutations (found in 20.2% of cases) impair RhoGAP activity, leading to aberrant RhoA activation and YAP-mediated oncogenic transformation 34. The gene is also implicated in developmental disorders, with damaging variants causing anophthalmia, microphthalmia, and coloboma, often with renal and neurological anomalies 5. Additionally, ARHGAP35 variants contribute to idiopathic hypogonadotropic hypogonadism by disrupting GnRH neuronal development 6. Ranking among the top 30 most frequently mutated genes across cancers, ARHGAP35 represents a critical regulatory node linking cytoskeletal dynamics to cell proliferation control 3.