Two pore segment channel 2 (TPCN2)

Two pore segment channel 2 (TPCN2), also known as TPC2, is a cation-selective ion channel primarily localized to lysosomal and late endosomal membranes[1][3][4]. TPCN2 is activated by the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) and/or phosphatidylinositol 3,5-bisphosphate (PI(3,5)P₂), depending on cell context, and mediates release of calcium ions from acidic organellar stores[1][4][5]. It differs structurally from other voltage-gated ion channels by having two homologous domains each with six transmembrane segments, forming a functional channel as a dimer[1][4]. TPCN2 plays key roles in intracellular signal transduction, especially in processes like autophagy, pigmentation, and cell trafficking, and it has been implicated in cancer, viral infections, and certain genetic disorders affecting pigmentation[4][5]. TPCN2 is pharmacologically tractable with small-molecule inhibitors studied in preclinical models for roles in cancer and viral pathogenesis, but no clinically approved drugs target TPCN2 yet. Its delicate involvement in lysosomal regulation and calcium signaling introduces safety challenges for therapeutic targeting[5].

Other names

Two pore channel protein 2TPC2Two pore calcium channel protein 2SHEP10voltage-dependent calcium channel protein TPC2

Allosteric inhibition of NAADP-induced calcium release; Inhibition of ion channel activity (Ca²⁺ or Na⁺ flow); Blockade of viral entry via endolysosomal disruption