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Nicotinic acid dinucleotide phosphate (NAADP) is unique amongst Ca(2+) mobilizing messengers in that its principal function is to mobilize Ca(2+) from acidic organelles. Early studies indicated that it was likely that NAADP activates a novel Ca(2+) release channel distinct from the well characterized Ca(2+) release channels on the (sarco)-endoplasmic reticulum (ER), inositol trisphosphate and ryanodine receptors. In this review, we discuss the emergence of a novel family of endolysosomal channels, the two-pore channels (TPCs), as likely targets for NAADP, and how molecular and pharmacological manipulation of these channels is enhancing our understanding of the physiological roles of NAADP as an intracellular Ca(2+) mobilizing messenger.

Original publication




Journal article


Sci China Life Sci

Publication Date





725 - 732


Animals, Calcium, Calcium Signaling, Cell Membrane, Endosomes, Humans, Ion Channel Gating, Ion Channels, Lysosomes, NADP