Schematic depiction of RAGE-ligand interaction showing domains of the receptor. The V-type domain is critical for binding of RAGE ligands. Deletion of the cytosolic tail results in a modified form of RAGE that binds ligands, remains firmly embedded in the cell membrane, but does not transmit RAGE-mediated cellular activation. Even in the presence of endogenous full-length RAGE, expression of dominant negative RAGE blocks signaling from the receptor. sRAGE, soluble RAGE (extracellular domain of RAGE); DN-RAGE, dominant negative RAGE (extracellular domain + transmembrane-spanning domain).