 Abstract vascular endothelial protein tyrosine phosphatase, VPTP, plays a key role in maintaining endothelial barrier function and preventing atherosclerosis. Exposure to high shear stress leads to VPTP degradation and T2 activation, which reduces plasma leakage and prevents atheroma formation. Blocking VPTP activity with a drug or genetic deletion can reduce atherosclerotic lesions in mice. These results suggest that VPTP could be a promising therapeutic target for treating atherosclerosis. This article was authored by Keisuke Shirakura, Peter Balak, Astrid F. Notaborn, and others.