TPC: the NAADP discovery channel?

The Ca²⁺-mobilizing second messenger, NAADP (nicotinic acid adenine dinucleotide phosphate), has been with us for nearly 20 years and yet we still cannot fully agree on the identity of its target Ca²⁺-release channel. In spite of some recent robust challenges to the idea that two-pore channels (TPCs) represent the elusive “NAADP receptor”, evidence continues to accumulate that TPCs are important for NAADP-mediated responses. This article will briefly outline the background and review more recent work pertaining to the TPC story.