Advanced glycosylation end product-specific receptor (AGER; RAGE) is a member of the immunoglobulin superfamily of cell surface molecules that binds molecules that have been irreversibly modified by non-enzymatic glycation and oxidation, and are know as advanced glycation end products (AGEs). It is expressed by endothelium, mononuclear phagocytes, neurons and smooth muscle cells. Whereas RAGE is present at high levels during development, especially in the central nervous system, its levels decline during maturity.The increased expression of RAGE is associated with several pathological states, such as diabetic vasculopathy, neuropathy, retinopathy and other disorders, including Alzheimer's disease and immune/inflammatory reactions of the vessel walls. In diabetic tissues, the production of RAGE is due to the overproduction of AGEs that eventually overwhelm the protective properties of RAGE. This results in oxidative stress and endothelial cell dysfunction that leads to vascular disease in diabetics. In the brain, RAGE also binds amyloid beta (Ab). Because Ab is overproduced in neurons and vessels in the brains of Alzheimer disease, this leads to the hyperstimulation of RAGE. The RAGE-Ab interaction is thought to result in oxidative stress leading to neuronal degeneration.