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In this review, we describe the background and implications of our recent discovery that two-pore channels (TPCs) comprise a novel class of calcium release channels gated by the intracellular messenger nicotinic acid adenine dinucleotide phosphate (NAADP). Their localisation to the endolysosomal system highlights a new function for these organelles as targets for NAADP-mediated Ca(2+) mobilisation. In addition, we describe how TPCs may also trigger further Ca(2+) release by coupling to the endoplasmic reticular stores through activation of IP(3) receptors and ryanodine receptors.

Original publication




Journal article


Pflugers Arch

Publication Date





869 - 876


Animals, Calcium Channels, Calcium Signaling, Endosomes, Humans, Ion Channel Gating, Lysosomes, Models, Molecular, NADP, Phylogeny