—Interest in the amyloid precursor protein (APP) initially arose in the study of Alzheimer’s disease, since amyloid β (Aβ), a product of proteolytic processing of APP, was considered key in the pathogenesis of this disease. However, subsequent more detailed and in-depth studies significantly expanded understanding of the functional spectrum of APP family proteins and demonstrated their involvement in many important physiological processes. Currently, APP is considered as a regulatory hub that forms a network of interacting proteins involved in synaptic and neural plasticity, which are a fundamental basis for learning, memory, cognition and behavior. This review analyzes and summarizes insights into the physiological role of the APP and its proteolytic fragments. Problems and the most promising areas for further development are also discussed.