Phospholipase A2 group VI (PLA2G6)

Phospholipase A2 group VI (PLA2G6) is a cytosolic, calcium-independent phospholipase A2 enzyme which catalyzes the hydrolysis of the sn-2 position of phospholipids, generating free fatty acids and lysophospholipids. It plays a key role in membrane phospholipid metabolism, maintaining membrane integrity, remodeling phospholipids, and regulating the release of bioactive lipid mediators such as arachidonic acid, which are important in inflammation and cell signaling. PLA2G6 is critical for normal neural function, and mutations in the PLA2G6 gene cause a spectrum of severe neurodegenerative disorders collectively known as PLA2G6-associated neurodegeneration (PLAN) or neurodegeneration with brain iron accumulation (NBIA), with infantile neuroaxonal dystrophy (INAD) being a well-known phenotype. There is also evidence linking phospholipid metabolism defects from PLA2G6 dysfunction with abnormal iron accumulation in the brain, Parkinsonian syndromes, and impaired cell signaling. As an intracellular enzyme with a broad biological role, PLA2G6 is studied as a potential therapeutic target, though currently there are no specific approved drugs targeting it. Genetic biomarkers (mutation analysis) and radiologic features support diagnosis in neurodegeneration cases. Inhibiting this enzyme carries risks of recapitulating the neurodegeneration phenotype seen in genetic disorders.

Other names

85/88 kDa calcium-independent phospholipase A2Group VI phospholipase A2Intracellular membrane-associated calcium-independent phospholipase A2 betaiPLA2-betaPatatin-like phospholipase domain-containing protein 9PNPLA9CaI-PLA2PLPLA9GVI PLA2iPLA2beta2-lysophosphatidylcholine acylhydrolaseNeurodegeneration with brain iron accumulation 2 protein (PLAN)PARK14NBIA2INAD1IPLA2-VIAPalmitoyl-CoA hydrolase

Inhibition of PLA2G6 would block the hydrolysis of the sn-2 acyl bond of phospholipids, reducing release of free fatty acids (like arachidonic acid), and thereby modulate downstream inflammatory lipid mediators