Rhes, also known as tumor endothelial marker 2 (TEM2), is a small GTP-binding protein that is predominantly expressed in the striatal region of the brain. This protein belongs to the RASD subfamily of Ras-related GTP-binding protein superfamily and is thought to play a role in the normal development and function of the brain as mice lacking this gene showed increased anxiety levels and motor coordination deficits. Rhes was identified as TEM2 through analysis of genes whose expression was upregulated in tumor endothelium. Tumor endothelial markers are significantly up-regulated during angiogenesis and neoangiogenesis that are crucial for the growth of solid tumors. TEMs localized on the cell surface and conserved across species are of particular interest for future development of anti-angiogenic therapies.