ARHGAP18 (Rho GTPase activating protein 18) functions as a negative regulator of Rho GTPases, particularly RhoA and RhoC, by enhancing their GTP hydrolysis and converting them to an inactive GDP-bound state 1. The protein plays critical roles in endothelial cell biology, where it is essential for flow-dependent endothelial cell alignment in the direction of blood flow, a protective response against atherosclerosis 23. ARHGAP18 deficiency leads to loss of endothelial alignment, disrupted cell junctions, and promotes pro-inflammatory phenotypes 2. The protein regulates cellular processes through multiple pathways, including the YAP signaling cascade, where ARHGAP18 acts upstream of YAP and controls its nuclear localization 3. In cancer contexts, ARHGAP18 exhibits complex, context-dependent roles. In hepatocellular carcinoma, it is upregulated by transcription factor GATA1 and promotes proliferation and invasion 4. In triple-negative breast cancer, ARHGAP18 overexpression paradoxically enhances metastasis by reducing RhoA activation 5. The protein also regulates endothelial permeability and inflammatory responses, with advanced glycosylation end products decreasing ARHGAP18 expression in diabetic complications 1. Additionally, ARHGAP18 appears protective in COPD, where miR-613-mediated upregulation inhibits cigarette smoke-induced apoptosis and epithelial-mesenchymal transition 6.