Dysregulation of membrane trafficking is observed in Alzheimer’s disease (Small and Gandy, 2006; Tan and Gleeson, 2019; Toh and Gleeson, 2016; Wang et al., 2024a) and includes defects in the trafficking of both APP and the secretases which result in elevated levels of APP processing and amyloid-β production. Here, APP is linked to early-onset autosomal dominant Alzheimer disease.