Members of the Ankyrin family of proteins mediate the attachment of integral membrane proteins to the cytoskeleton. ANK1, ANK2 and ANK3 genes encode for the proteins in this family, Ankyrin-1 (also designated Ankyrin R), Ankyrin B and Ankyrin G, respectively. The proteins are structured similarly each composed of an N-terminal domain with multiple ankyrin repeats, a highly conserved central spectrin binding domain, and C-terminal regulatory domains which are susceptible to the most variance. Both Ankyrin B and Ankyrin G are essential for normal neuronal functions. Ankyrin B, or brain Ankyrin is predominantly expressed in the plasma membrane of neurons as well as glial cells throughout the brain. Two transcripts have been described with alternative splicing resulting in additional isoforms. The Ankyrin B protein associates with the spectrin-actin network, mediates axon fasciculation, and stabilizes axon bundles. Ankyrin B is required for coordinated assembly of Na/Ca exchanger, Na/K ATPase, and inositol trisphosphate (InsP(3)) receptor at transverse-tubule/sarcoplasmic reticulum sites in cardiomyocytes.