Cytosolic phospholipase A2 group IVA (cPLA2)

Cytosolic phospholipase A2 (cPLA2), particularly the Group IVA isoform (cPLA2α), is a pivotal intracellular enzyme that serves as a primary regulator of the arachidonic acid cascade [7, 21]. It catalyzes the hydrolysis of membrane phospholipids at the sn-2 position, specifically releasing arachidonic acid—the rate-limiting precursor for the biosynthesis of potent bioactive lipid mediators such as prostaglandins, leukotrienes, and thromboxanes [6, 15]. Activated by sub-micromolar concentrations of calcium and post-translational phosphorylation, cPLA2 translocates from the cytosol to the nuclear envelope and endoplasmic reticulum to initiate signaling [15, 21]. Due to its central role in generating pro-inflammatory mediators, it is a major therapeutic target for inflammatory disorders like rheumatoid arthritis and asthma, as well as neurodegenerative diseases and certain cancers where lipid signaling promotes tumor growth [9, 11, 18]. Pharmacological inhibition of cPLA2 offers a strategic advantage over downstream targets by concurrently blocking multiple inflammatory pathways, although its roles in physiological processes like reproduction present distinct therapeutic challenges [13, 23].

Other names

cPLA2-alphaPLA2G4APhospholipase A2 group IVAPhosphatidylcholine 2-acylhydrolaseLysophospholipaseCellular phospholipase A2

Inhibition of the enzyme-mediated hydrolysis of the sn-2 ester bond of membrane phospholipids, which prevents the release of arachidonic acid and the subsequent production of pro-inflammatory eicosanoids such as prostaglandins and leukotrienes.