ARHGAP17 is a Rho GTPase-activating protein that inactivates CDC42 and RAC1 to regulate epithelial cell polarity and cytoskeletal organization. It maintains tight junction integrity by controlling the spatial distribution of CDC42 activity and works with AMOT to regulate recycling of polarity proteins at junctions. Beyond epithelial homeostasis, ARHGAP17 functions as a tumor suppressor across multiple cancer types. In cervical cancer, reduced ARHGAP17 expression correlates with malignancy; restoration of expression suppresses cell proliferation by inhibiting PI3K/AKT signaling and upregulating the cell cycle inhibitors P21 and P27 1. In colon cancer, ARHGAP17 suppresses tumor growth and metastasis through inactivation of Wnt/β-catenin signaling and enhances chemosensitivity to 5-fluorouracil by suppressing Rac1 23. Similarly, in hepatocellular carcinoma, ARHGAP17 inhibits progression by dampening Wnt/β-catenin pathway activation 4. In non-malignant contexts, ARHGAP17 protects intestinal barrier integrity 5, prevents mechanically-induced apoptosis in periodontal ligament fibroblasts 6, and regulates invadopodia turnover in breast cancer cells by controlling spatiotemporal CDC42 activity 7. Cerebellar development requires ARHGAP17-mediated RAC1 activation downstream of WDR4 8. These diverse roles establish ARHGAP17 as a central regulator of GTPase signaling with broad implications for development, tissue homeostasis, and cancer biology.