N-terminal tagging of two-pore channels interferes with NAADP action.

NAADP (nicotinic acid-adenine dinucleotide phosphate) is the most potent Ca2+-releasing second messenger known to date. Since its discovery in 1995 identifying the NAADP receptor protein/Ca2+ channel has been a major persuit of the Ca2+ signalling community. In their paper 'The N-terminal region of two-pore channel 1 regulates trafficking and activation by NAADP' published in this issue of the Biochemical Journal Patel and colleagues describe that the N-terminus of one of the NAADP receptor protein/Ca2+ channel candidates, TPC1 (two-pore channel 1), is crucial for protein targeting and for sensitivity to NAADP.