This minireview by Gopal Thinakaran and Edward H. Koo from the University of Chicago and the University of California, San Diego, provides an overview of the intracellular trafficking, proteolytic processing, and biological functions of amyloid precursor protein (APP). APP is the precursor to the amyloid β-protein (Aβ), which is central to the amyloid cascade hypothesis of Alzheimer's disease (AD). The review highlights the significant progress made in understanding APP processing, including the identification of secretases involved in Aβ production and the role of APP gene family members. APP is processed through β- and γ-secretase cleavages, generating Aβ and other products like the intracellular APP-β-cleaved fragment (AICD). The review also discusses the intracellular itinerary of APP, its trophic properties, and its role in cell adhesion. APP has been shown to stimulate neurite outgrowth and synaptogenesis, and its deficiency in mice leads to developmental abnormalities and cognitive deficits. The review concludes by emphasizing the importance of APP in AD pathogenesis and the need for further research into its normal functions.This minireview by Gopal Thinakaran and Edward H. Koo from the University of Chicago and the University of California, San Diego, provides an overview of the intracellular trafficking, proteolytic processing, and biological functions of amyloid precursor protein (APP). APP is the precursor to the amyloid β-protein (Aβ), which is central to the amyloid cascade hypothesis of Alzheimer's disease (AD). The review highlights the significant progress made in understanding APP processing, including the identification of secretases involved in Aβ production and the role of APP gene family members. APP is processed through β- and γ-secretase cleavages, generating Aβ and other products like the intracellular APP-β-cleaved fragment (AICD). The review also discusses the intracellular itinerary of APP, its trophic properties, and its role in cell adhesion. APP has been shown to stimulate neurite outgrowth and synaptogenesis, and its deficiency in mice leads to developmental abnormalities and cognitive deficits. The review concludes by emphasizing the importance of APP in AD pathogenesis and the need for further research into its normal functions.