The proteolytic processing and secretion of APP are regulated by protein phosphorylation, especially via protein kinase C and protein phosphatases 1 and/or 2A. Our studies of these regulatory mechanisms have led us to perform extensive experimentation on the metabolism of APP carboxyl-terminal fragments, using as our system either untransfected, undifferentiated rat pheochromocytoma (PC12) cells or APP-baculovirus infected Sf9 cells. We have not assayed APP fragments for biological activity in either system. However, we have made potentially relevant observations regarding APP carboxyl-terminal fragment trafficking. In this note, we review our published and unpublished data in relation to published reports from other laboratories using related systems.