Spectrins are central components of the cytoskeleton that form a scaffold below the plasma membrane. Spectrins contain two subunits, alpha and ß, which intertwine to form heterodimers that can self associate into elongated tetramers. alpha-spectin I and ß-spectrin I form heterodimers in red blood cells, while nonerythroid mammalian cells contain heterodimers of alpha-spectin I and II with ß-spectrin I to V. The structure of spectrins includes a succession of triple-helical repeats alongwith various domains, such as SH3 domain, EF hands, PH domains, and binding domains for ankyrin, actin, band 4.1, and calmodulin. alpha-spectrin II is a widely expressed non-erythroid alpha-spectrin that contains an SH3 domain, a calmodulin binding site, and two cleavage sites for proteases, such as calpains and caspase-3. ß-spectrin II is a widely expressed non-erythroid ß-spectrin that contains a C-terminal region that interacts with alpha-spectrins and a PH domain. alpha-spectrin II and ß-spectrin II, like many other spectrins, can form heterodimers that can self associate into tetramers, as well as interact with Band 4.1, F-actin, and other proteins near the plasma membrane. This scaffold of cytoskeletal and plasma membrane proteins is critical for the maintenance of cell structure.