The Ryanodine Receptor (RyR) is the channel responsible for calcium release from muscle cell Sarcoplasmic Reticulum (SR) and also plays a role in calcium regulation in non-muscle cells. The RyR exists as a homotetramer and is predicted to have a short cytoplasmic C-terminus and 4-10 transmembrane domains. The remainder of the protein, termed the "foot" region, is located in the cytoplasm between the transverse tubule and the SR. Mammalian RyR isoforms are the product of three different genes: RyR-1 is expressed predominantly in skeletal muscle and areas of the brain; RyR-2 is expressed predominantly in heart muscle but also found in the stomach, endothelial cells and diffuse areas of the brain; and RyR-3 is found in smooth muscle and the brain (striatum, thalamus and hippocampus). In non-mammalian vertebrates, the RyR isoforms are termed alpha, beta and cardiac which correlate loosely to the mammalian RyR-1, RyR-3 and RyR-2 isoforms respectively.