Two-pore channels (TPCs) are adenine nucleotide and phosphoinositide regulated cation channels. NAADP activates and ATP blocks TPCs, while the endolysosomal phosphoinositide PI(3,5)P(2) activates TPCs. TPCs are ubiquitously expressed including expression in the innate as well as the adaptive immune system. In the immune system TPCs are found, e.g. in macrophages, mast cells and T cells. In cytotoxic T cells, NAADP activates TPCs on cytolytic granules to stimulate exocytosis and killing. …