The β-isoform of group VIA calcium-independent phospholipase A 2 (iPLA2β) does not require calcium for activation, is stimulated by ATP, and is sensitive to inhibition by a bromoenol lactone suicide substrate. Several potential functions have been proposed for iPLA 2β. Our studies indicate that iPLA2β is expressed in β-cells and participates in glucose-stimulated insulin secretion but is not involved in membrane phospholipid remodeling. If iPLA 2β plays a signaling role in glucose-stimulated insulin secretion, then conditions that impair iPLA2β functions might contribute to the diminished capacity of β-cells to secrete insulin in response to glucose, which is a prominent characteristic of type 2 diabetes. Our recent studies suggest that iPLA2β might also participate in β-cell proliferation and apoptosis and that various phospholipid-derived mediators are involved in these processes. Detailed characterization of the iPLA2β protein level reveals that β-cells express multiple isoforms of the enzyme, and our studies involve the hypothesis that different isoforms have different functions.