Calcium (Ca²⁺) is a major signaling molecule that activates an array of cellular events. Accordingly, cytosolic Ca²⁺ levels are tightly controlled at approximately 100 nM. However, elevations to approximately 300 nM initiate powerful signals that control a spectrum of cell functions, ranging from short-term contractile responses to long-term events such as transcription. Thus, maintenance of cytosolic Ca²⁺ is a very important and elaborate process. Some of the regulatory elements that maintain these cytosolic Ca²⁺ levels are ion channels and exchangers located on the plasma membrane of the cell. However, the endoplasmic reticulum (ER) also plays a large role in Ca²⁺ signaling. The ER lumen stores approximately 500 μM of Ca²⁺, which not only provides an environment conducive for proper protein folding, but also serves as a major source of Ca²⁺ for signaling.