PNPLA6 encodes Neuropathy Target Esterase (NTE), a phospholipase B that catalyzes deacylation of phosphatidylcholine (PtdCho) at both sn-2 and sn-1 positions, generating glycerophosphocholine 1. The enzyme hydrolyzes lysophospholipids and monoacylglycerols with preference for 1-acyl isomers, functioning primarily in endoplasmic reticulum membranes to maintain phospholipid homeostasis 2. Recently, mechanistic studies revealed PNPLA6 regulates retinal homeostasis by mobilizing choline from phosphatidylcholine for phospholipid recycling in retinal pigment epithelial cells, which supply choline to adjacent photoreceptors for survival 3. Biallelic pathogenic PNPLA6 variants cause five systemic neurological disorders: spastic paraplegia type 39, Gordon-Holmes, Boucher-Neuhäuser, Laurence-Moon, and Oliver-McFarlane syndromes, characterized by gait disturbance, chorioretinal dystrophy, anterior hypopituitarism, and hair anomalies 4. Disease phenotypes exhibit a striking inverse relationship with NTE enzymatic activity; individuals with lower NTE activity develop retinopathy and endocrinopathy, establishing an NTE activity threshold for disease manifestation 5. Animal models demonstrate loss-of-function mechanisms, and delayed therapeutic induction of NTE function can ameliorate neurodegeneration even after symptom onset, suggesting treatment windows may exist 6.