Phosphoprotein enriched in astrocytes 15(PEA15) was initially identified in astrocytes. PEA15, also known as phosphoprotein enriched in diabetes (PED), is a small protein involved in many protein-protein interactions that modulate the function of some key cellular effectors involved in major cell functions, including apoptosis, proliferation, and glucose metabolism. In particular, PED/PEA15 interacts with the phospholipase D (PLD) isoforms 1 and 2 increasing protein kinase C-α isoform activity and affects both insulin-stimulated glucose transport and glucose-stimulated insulin secretion. PEA15 binds ERK and RSK2 and high PEA15 levels can impair ERK- and RSK2-dependent transcription. PEA15 expression also inversely correlates with cell motility and invasiveness. Phosphoprotein enriched in astrocytes 15 (PEA15) plays a multi-functional role in neuronal cell survival.