These in vivo findings support the idea that APPL1 recruitment to early endosomes is sufficient to replicate endosomal, functional, and neurodegenerative changes induced by elevated APP-βCTF levels and rab5 overactivation in AD and related animal models (Jiang et al., 2016, 2019, 2022; Pensalfini et al., 2020; Peng et al., 2024). Here, APPL1 is linked to Alzheimer disease.