Cytosolic phospholipase A2 Group IVA (cPLA2) (cPLA2)

Cytosolic phospholipase A2 Group IVA (cPLA2) is a calcium-dependent enzyme that serves as the primary regulator of the eicosanoid cascade by selectively hydrolyzing the sn-2 position of membrane phospholipids. This catalytic activity releases arachidonic acid, the critical precursor for the biosynthesis of potent lipid mediators such as prostaglandins, leukotrienes, and thromboxanes. Beyond its central role in inflammatory signaling, cPLA2 is involved in diverse cellular processes, including membrane remodeling, signal transduction, and the maintenance of autophagic flux. Dysregulation of this enzyme is implicated in the pathogenesis of chronic inflammatory conditions like rheumatoid arthritis and asthma, as well as neurodegenerative disorders and cardiovascular diseases. In oncology, cPLA2 is often overexpressed and contributes to tumor cell proliferation, survival, and metastasis. Therapeutic targeting of cPLA2 with small-molecule inhibitors aims to dampen the systemic inflammatory response at its source. However, development has been hindered by challenges such as gastrointestinal toxicity and the need for high selectivity over other phospholipase isoforms to avoid off-target effects.

Other names

PLA2G4AGroup IVA phospholipase A2cPLA2-alpha85 kDa cytosolic phospholipase A2Phosphatidylcholine 2-acylhydrolase

Selective inhibition of the cPLA2 enzyme, which prevents the hydrolysis of membrane phospholipids at the sn-2 position, thereby blocking the rate-limiting release of arachidonic acid and the subsequent production of pro-inflammatory eicosanoids.