(A) Top view of the dimeric structure of hTPC2 in a POPC membrane; the two subunits are shown in red and green. (B) The pore-forming domain (purple) and voltage-sensing domains (orange) are highlighted within the two subunits of hTPC2. (C) Location of hTPC2 in the endolysosomal membrane and direction of ion flux from the endolysosomal lumen to the cytosol. (D) Schematic of the pore architecture of hTPC2. The panel shows a slice through the pore domain; the inner pore is formed by helices S6 from 6-TM-I and 6-TM-2 of each subunit, and the selectivity filter (pore entrance) is located in a loop section between the pore helices P1 and P2 from 6-TM-I and 6-TM-2 of each subunit.