The N-terminal region of two-pore channel 1 regulates trafficking and activation by NAADP

TPCs (two-pore channels) are NAADP (nicotinic acid–adenine dinucleotide phosphate)-sensitive Ca²⁺-permeable ion channels expressed on acidic organelles. In the present study we show that deletion of the N-terminal region redirects TPC1 to the ER (endoplasmic reticulum). The introduction of fluorophores at the N-terminus of TPC1 does not affect its subcellular location, but does reversibly abolish NAADP sensitivity. Our results reveal a dual role for the N-terminus in localization and function of TPC1.