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The endoplasmic reticulum (ER) is not simply a uniform continuous organelle, but is spatially and functionally heterogeneous with nonuniform distribution of endoplasmic Ca2+-handling proteins, such as Ca2+-binding proteins, Ca2+ pumps, and Ca2+-release channels. Such nonuniform distribution of Ca2+-handling proteins is thought to create a spatially divided calcium store and to contribute to the generation of complex intracellular Ca2+ dynamics. In addition to the particular distribution of these Ca2+-handling proteins within ER, extracellular stimuli may also stimulate the formation of dynamic new ER compartments containing Ca2+-handling proteins. These compartments containing Ca2+-handling proteins have potential roles in Ca2+ signaling; specifically, they may function as "induced coupling domains" between the ER and plasma membrane, thereby allowing Ca2+ entry into the ER.