Cells utilize calcium ions (Ca2+) to signal almost all aspects of cellular life,ranging from cell proliferation to cell death,in a spatially and temporally regulated manner.A key aspect of this regulation is the compartmentalization of Ca2+ in various cytoplasmic organelles that act as intracellular Ca2+ stores.Whereas Ca2+ release from the large-volume Ca2+ stores,such as the endoplasmic reticulum (ER) and Golgi apparatus,are preferred for signal transduction,Ca2+ release from the small-volume individual vesicular stores that are dispersed throughout the cell,such as lysosomes,may be more useful in local regulation,such as membrane fusion and individualized vesicular movements.Conceivably,these two types of Ca2+ stores may be established,maintained or refilled via distinct mechanisms.ER stores are refilled through sustained Ca2+ influx at ER-plasma membrane (PM) membrane contact sites (MCSs).In this review,we discuss the release and refilling mechanisms of intracellular small vesicular Ca2+ stores,with a special focus on lysosomes.Recent imaging studies of Ca2+ release and organelle MCSs suggest that Ca2+ exchange may occur between two types of stores,such that the small stores acquire Ca2+ from the large stores via ER-vesicle MCSs.Hence vesicular stores like lysosomes may be viewed as secondary Ca2+ stores in the cell.