Calcium-independent phospholipase A2 group VI (PLA2G6) (iPLA2-beta)

Calcium-independent phospholipase A2 group VI (PLA2G6), commonly known as iPLA2-beta, is an 85/88 kDa enzyme that plays a central role in cellular lipid metabolism by catalyzing the hydrolysis of the sn-2 ester bond of phospholipids (UniProt P39755). This activity releases free fatty acids, such as arachidonic acid, and lysophospholipids, which are essential for membrane remodeling via the Lands' cycle and for various intracellular signaling pathways (NCBI Gene ID: 5337). Unlike many other phospholipases, iPLA2-beta does not require calcium for its catalytic activity and is regulated by ATP binding and protein-protein interactions. It is highly expressed in the brain and is critical for maintaining mitochondrial integrity and axonal health. Mutations in the PLA2G6 gene are the primary cause of PLA2G6-associated neurodegeneration (PLAN), a spectrum of disorders including infantile neuroaxonal dystrophy (INAD) and early-onset Parkinson's disease (PubMed PMID: 20301718). Due to its involvement in inflammatory signaling and neurodegenerative processes, iPLA2-beta is a significant target for pharmacological research, with small-molecule inhibitors being explored for potential therapeutic applications in neurodegeneration and inflammation.

Other names

85/88 kDa calcium-independent phospholipase A2Group VIA phospholipase A2iPLA2-betaPLA2G6PNPLA9Calcium-independent phospholipase A2-betaPatatin-like phospholipase domain-containing protein 9

Inhibition of the enzyme's catalytic site to prevent the hydrolysis of phospholipids and the subsequent release of pro-inflammatory or signaling lipid mediators.