Pla2G6 — Phospholipase A2 Group Vi is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
PLA2G6 (Phospholipase A2 Group VI), also known as iPLA2-VI or iPLA2, is a calcium-independent phospholipase that hydrolyzes the sn-2 position of phospholipids to release fatty acids and lysophospholipids. Located on chromosome 22q13.1, this gene encodes a 752-amino acid protein predominantly expressed in the brain, particularly in regions vulnerable to neurodegeneration[1].
PLA2G6 belongs to the group VI of phospholipases A2, which are characterized by their lack of calcium dependence for catalytic activity. The enzyme plays important roles in membrane phospholipid remodeling, fatty acid signaling, and the generation of bioactive lipid mediators. In neurons, PLA2G6 is involved in regulating membrane fluidity, synaptic function, and responses to oxidative stress[2].
Mutations in PLA2G6 cause a spectrum of neurodegenerative disorders, including infantile neuroaxonal dystrophy (INAD), PLAN (PLA2G6-associated neurodegeneration), and early-onset Parkinson's disease. These conditions share features of progressive motor and cognitive decline, reflecting the protein's essential role in neuronal survival[3].
— Phospholipase A2 Group VI
Phospholipase A2 Group VI (PLA2G6) encodes iPLA2-VIA, a calcium-independent phospholipase A2 enzyme that hydrolyzes the sn-2 position of phospholipids to release free fatty acids and lysophospholipids 1(https://pubmed.ncbi.nlm.nih.gov/10436031/). This enzyme plays crucial roles in membrane remodeling, lipid signaling, and cellular homeostasis.
Rare heterozygous PLA2G6 mutations have been associated with late-onset Parkinson's disease, typically with atypical features 2(https://pubmed.ncbi.nlm.nih.gov/20683658/). The role of PLA2G6 in sporadic PD remains under investigation.
Biallelic PLA2G6 mutations cause INAD, a progressive neurodegenerative disorder characterized by:
This umbrella term includes INAD and milder phenotypes with later onset:
PLA2G6 is widely expressed:
Last updated: 2026-03-03
The study of Pla2G6 — Phospholipase A2 Group Vi has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.