Deyts et al. (2019) revealed that APP-mediated signaling through a direct interaction with the G-protein alpha subunit prevents memory and cognitive decline in an AD mouse model. Recently, Bose et al. (2021) reported that dysfunction of endosomal and lysosomal CLC chloride transporters results in neurodegeneration in mice and humans. Cell-cell junctions have been shown to be related to the AD-related presenilin 1 gene (Singh et al., 2001). Here, APP is linked to Alzheimer disease.