Through the probing of recent findings, which are primarily utilized to elucidate the defective intracellular trafficking as a neurodegenerative mechanism in AD (Kim et al., 2016; Xu et al., 2016; Kwart et al., 2019; Knupp et al., 2020; Hung et al., 2021; Mishra et al., 2022), here I explain that APP signaling in endosomes is critical for its remodeling-related function. This evidence concerns the gene APP and Alzheimer disease.