The accumulation of Aβ/APP-CTF promotes neuropathy by eliciting endosomal abnormality and Rab5 overactivation, and compromising lysosomal calcium stores through inhibition of lysosome–endoplasmic reticulum contacts in PSEN1-knockout or mutant mouse neurons, or human induced neurons45,69–71. Here, PSEN1 is linked to neuropathy.