RAB5A and Alzheimer disease: 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.