PSEN1 and Alzheimer disease: Whereas Lee, Nixon and colleagues have put forward a hypothesis according to which pH defects would initiate endolysosomal defects in the context of AD through a PSEN1-dependent recruitment of the lysosomal v-ATPase proton pump (Lee et al., 2015), other research groups could not confirm this (Coen et al., 2012; Zhang et al., 2012), and showed instead impaired LE/Lys Ca2+ as the triggering factor of endolysosomal demise (Coen et al., 2012; Zhang et al., 2012; Peric and Annaert, 2015).