Two pore segment channel 1 (TPCN1)

Two pore segment channel 1 (TPCN1) is an intracellular voltage-gated ion channel, encoded by the TPCN1 gene in humans, and belongs to the two-pore channel (TPC) family. Unlike conventional calcium and sodium channels, which have four homologous domains, TPCN1 contains only two domains, each with six transmembrane segments. TPCN1 is mainly localized to early and recycling endosomal membranes, where it regulates organellar membrane excitability, ion transport, membrane trafficking, and pH homeostasis. It is activated by NAADP and PI(3,5)P2, with ion selectivity that is agonist-dependent—acting as either a calcium- or sodium-permeable channel. TPCN1 plays important roles in mTOR-dependent nutrient sensing and is critical for the entry of filoviruses (e.g., Ebola, Marburg) and other pathogens by controlling endosomal trafficking. Disease associations include nephrotic syndromes, hemoglobinopathies, Parkinson's disease, and metabolic disorders such as fatty liver. Pharmacological blockade of TPCN1 impedes viral infection and may have therapeutic relevance, but also poses risks due to its role in essential cellular processes.

Other names

Two pore channel protein 1TPC1KIAA1169FLJ20612Two pore calcium channel protein 1Voltage-dependent calcium channel protein TPC1

Blockade of channel function (inhibition of ion conductance), prevents viral endosomal escape. Antagonism of NAADP-mediated calcium release.