Amyloid precursor protein (APP) fascinates cell biologists because it is proteolytically processed to generate multiple peptides, including amyloid-β, which is implicated in Alzheimer's disease. However, a large body of data also shows that the extracellular soluble fragment of APP produced by α-secretase (sAPPα) is neuroprotective and promotes neuronal outgrowth. A study by Demars and colleagues appearing in the previous issue provides data showing that sAPPα is a general growth factor for stem cells of multiple lineages. Thus, APP seems to play complex and disparate roles in neurodegeneration and neuroprotection.