Patatin-like phospholipase domain-containing protein 6 (PNPLA6)

Patatin-like phospholipase domain-containing protein 6 (PNPLA6), also known as neuropathy target esterase (NTE), is a membrane-associated serine hydrolase enzyme located at the cytoplasmic face of the endoplasmic reticulum, most abundant in neurons. It catalyzes the deacylation of phosphatidylcholine and lysophosphatidylcholine, playing a critical role in phospholipid homeostasis, axonal maintenance, and hormone release. Loss-of-function mutations in PNPLA6 are causative for diverse syndromic neurodegenerative and endocrine disorders, including hereditary spastic paraplegia type 39, Gordon-Holmes syndrome, and Boucher-Neuhäuser syndrome. As a phospholipase, NTE is a noted molecular target for organophosphate toxins, which cause delayed neuropathy through enzyme inhibition. NTE activity is used as a diagnostic biomarker and is a potential therapeutic target, but safety concerns arise because inhibition or perturbation can lead to severe neurological and systemic effects

Other names

Neuropathy target esteraseNTEiPLA2deltaSpastic paraplegia type 39 protein (SPG39)swsBNHSLNMSOMCSNTEMNDOliver-McFarlane syndrome proteinBoucher-Neuhäuser syndrome proteinGordon-Holmes syndrome protein

Inhibition of PNPLA6/NTE leads to phospholipid dysregulation, axonal degeneration, and impaired hormone release