The amyloid precursor protein (APP) gene and its protein products have multiple functions in the central nervous system and fulfil criteria as neuractive peptides: presence, release and identity of action. There is increased understanding of the role of secretases (proteases) in the metabolism of APP and the production of its peptide fragments. The APP gene and its products have physiological roles in synaptic action, development of the brain, and in the response to stress and injury. These functions reveal the strategic importance of APP in the workings of the brain and point to its evolutionary significance.