Calcium ions act as second messengers to control a broad range of physiological effects. Deregulation of intracellular calcium levels can result in irreversible injury and has been implicated in several disease conditions. Thus, calcium homeostasis, the control of intracellular Ca2+ concentration, is very tightly regulated. Calcium functions as an effector signaling molecule by modulating the function of intracellular enzymes and voltage-gated ion channels. Calcium-binding proteins are critical for the second messenger effects of intracellular calcium. For example, the S100 (soluble in 100% saturated ammonium sulfate) family of vertebrate EF-hand Ca2+-binding proteins influence diverse biological processes including cell cycle progression, cell growth, cell motility, transcription and cell differentiation. Calsyntenin is expressed in the ER/Golgi and on the plasma membranes of almost all neurons. It is a calcium-binding protein that may regulate postsynaptic signaling and APP cleavage. In presynaptic vesicles, Synaptotagmin, a highly conserved calcium-binding protein, facilitates neurotransmitter release by triggering exocytosis.