Given that directly hyperactivating rab5 in vivo in mice via modest neuronal overexpression of rab5 recapitulates AD-related endosome anomalies and their neurodegenerative consequences (Kim et al., 2016; Pensalfini et al., 2020), we investigated whether APPL1 stabilization of active rab5 induces similar pathologies, thereby linking APPL1 elevation seen in AD (Johnson et al., 2022) and early endosome pathobiology. This evidence concerns the gene APPL1 and Alzheimer disease.