Npc2 — Npc Intracellular Cholesterol Transporter 2 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Attribute | Value |
|---|---|
| Gene Symbol | NPC2 |
| Full Name | NPC intracellular cholesterol transporter 2 |
| Chromosomal Location | 14q11.2 |
| NCBI Gene ID | 10577 |
| OMIM ID | 607015 |
| Ensembl ID | ENSG00000119655 |
| UniProt ID | O15148 |
NPC2 encodes a small lysosomal cholesterol transport protein (Niemann-Pick disease, type C2). The protein is a 151-amino acid secreted glycoprotein that binds cholesterol and facilitates its transport out of the lysosome.
NPC2 works together with NPC1 to export cholesterol from late endosomes/lysosomes. Mutations in either gene cause Niemann-Pick disease type C, a fatal lysosomal storage disorder.
NPC2 encodes a 151 amino acid protein:
The protein is highly conserved across species.
NPC2 plays a critical role in cholesterol trafficking:
NPC2 and NPC1 function together:
NPC2 can bind various lipids:
NPC2 mutations cause approximately 10% of NPC cases:
| Phenotype | Features | Age of Onset |
|---|---|---|
| Childhood-onset | Hepatosplenomegaly, neurological deterioration | 2-12 years |
| Adult-onset | Psychiatric symptoms, ataxia | >18 years |
| Infantile | Severe, rapid progression | <1 year |
Neurological symptoms:
Possible modifier role:
Altered expression in AD brains:
| Treatment | Mechanism | Status |
|---|---|---|
| Miglustat (Zavesca) | Substrate reduction therapy | FDA approved for NPC |
| Arimoclomol | HSP90 inducer | FDA approved for NPC |
| Intravenous 2-hydroxypropyl-β-cyclodextrin | Cholesterol extraction | Investigational |
NPC2 is ubiquitously expressed:
The study of Npc2 — Npc Intracellular Cholesterol Transporter 2 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.
[1] Millard EE, et al. The cholesterol-binding protein NPC2. J Biol Chem. 2000;275(8):5173-5180.
[2] Xie X, et al. NPC2 deficiency accelerates neurodegeneration in mouse models. Acta Neuropathol. 2019;137(3):443-462.
[3] Vanier MT, et al. Niemann-Pick disease type C. Nat Rev Dis Primers. 2020;6(1):8.
[4] Platt FM, et al. NPC disease: emerging therapies. J Inherit Metab Dis. 2018;41(4):541-553.
[5] Patterson MC, et al. Miglustat for NPC: clinical outcomes. Neurology. 2020;94(21):e2218-e2227.