The Notch receptors are highly conserved from invertebrates to mammals. Notch 1 and Notch 2 exhibit the greatest structural similarity among the four mammalian Notch receptors. Notch 3 has a number of structural and functional differences. The binding of Notch 3 to its ligands results in the proteolysis of Notch and movement of intracellular portions of Notch into the nucleus. This translocation triggers a series of signaling processes. Notch 3 is primarily expressed in adult arterial smooth muscle cells. Notch 3 gene mutation can cause CADASIL, an inherited early stroke syndrome.