Intracellular channel initially characterized as a non-selective Ca(2+)-permeable channel activated by NAADP (nicotinic acid adenine dinucleotide phosphate), it is also a voltage-gated highly-selective Na(+) channel activated directly by PI(3,5)P2 (phosphatidylinositol 3,5-bisphosphate) that senses pH changes and confers electrical excitability to organelles. Localizes to the early and recycling endosomes membranes where it plays a role in the uptake and processing of proteins and regulates organellar membrane excitability, membrane trafficking and pH homeostasis. Ion selectivity is not fixed but rather agonist-dependent and under defined ionic conditions, can be readily activated by both NAADP and PI(3,5)P2. Required for mTOR-dependent nutrient sensing. Na(+)(in) = Na(+)(out) Ca(2+)(in) = Ca(2+)(out) Na(+) current is inhibited by ATP in a MTORC-dependent manner. ATP sensitivity is independent of PI(3,5)P2 (By similarity). Probably regulated by Mg(2+) ions, cytosolic Mg(2+) selectively inhibits outward current while lysosomal Mg(2+) modestly inhibits both the outward and inward currents. In the absence of Mg(2+), NAADP readily activates TPCN2, with properties similar to PI(3,5)P2 (By similarity). Both current elicited by PI(3,5)P2 as well as NAADP are inhibited by tetrandrine (By similarity). Dimer. Interacts with MTOR; the interaction is required for TPCN1 ATP sensitivity (By similarity). Interacts with STX7, STX8 and STX12 (By similarity). Interacts with JPT2 (By similarity). Found in a complex with LSM12, TPCN1 and TPCN2 (By similarity). Widely expressed. Expressed at relatively high level in kidney, liver and lung, and in the kidney it is expressed at inner medullary collecting ducts. Each of the two internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position. N-glycosylated. Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. Two pore calcium channel subfamily.