Many cells express a Group VIA phospholipase A2, designated iPLA2β, that does not require calcium for activation, is stimulated by ATP, and is sensitive to inhibition by a bromoenol lactone suicide substrate (BEL). Studies in various cell systems have led to the suggestion that iPLA2β has a role in phospholipid remodeling, signal transduction, cell proliferation, and apoptosis. We have found that pancreatic islets, β-cells, and glucose-responsive insulinoma cells express an iPLA2β that participates in glucose-stimulated insulin secretion but is not involved in membrane phospholipid remodeling. Additionally, recent studies reveal that iPLA2β is involved in pathways that contribute to β-cell proliferation and apoptosis, and that various phospholipid-derived mediators are involved in these processes. Detailed characterization of the enzyme suggests that the β-cells express multiple isoforms of iPLA2β, and we hypothesize that these participate in different cellular functions.