Pla2g6, the phospholipase A2 group VI gene, encodes an enzyme involved in membrane homeostasis, signal transduction, mitochondrial dysfunction, and α -synuclein aggregation [1]. It belongs to the PLA2 superfamily and catalyzes the hydrolytic release of fatty acids from phospholipids, being essential for remodeling membrane phospholipids in axons and synapses in the nervous system [2].

In the PLA2G6 knockout (KO) mouse, an excellent model for studying PLA2G6-associated neurodegeneration (PLAN), specific membrane degeneration occurs in neurons and their axons, followed by axonal spheroid formation. From a young age, many mitochondria with damaged inner membranes appear in KO mouse neurons, which move anterogradely in axons. As membrane degeneration progresses, axonal injury occurs near impaired mitochondria. At axon terminals, the presynaptic membranes expand irregularly and eventually rupture [2].

In conclusion, Pla2g6 is crucial for membrane phospholipid remodeling in the nervous system. The PLA2G6 KO mouse model has been instrumental in revealing the role of Pla2g6 in membrane degeneration processes underlying PLAN, Parkinson disease, and neurodegeneration with iron accumulation (NBIA), all of which are assumed to involve primary axon degeneration [2].