On balance, the controversy has been somewhat resolved and it is clear that TPCs are absolutely essential for NAADP. The permeability properties are more equivocal: why some groups observe a Na+ selectivity while others see a mixed Na+/Ca2+ permeability is currently unclear. The necessarily artificial experimental conditions for such as a demanding technique as single-lysosome patch clamp makes it harder to be dogmatic about which ions permeate under native, physiological conditions. It is likely (and the simpler model) that TPCs function as NAADP-gated Ca2+-permeable channels, but it cannot be formally excluded that TPCs, acting as Na+ channels, play a permissive role in a more complex ionic circuit that supports NAADP-induced Ca2+ release [https://www.ncbi.nlm.nih.gov/pubmed/24277557][https://www.ncbi.nlm.nih.gov/pubmed/26009180].