NRAS

NPC2 (Niemann-Pick disease, type C2) is a protein that in humans is encoded by the NPC2 gene. This protein is involved in the intracellular transport of cholesterol and other lipids. It plays a crucial role in the lysosome where it binds cholesterol and facilitates its transfer to the NPC1 protein, which then transports cholesterol out of the lysosome.

Function

NPC2 is a small, soluble protein that binds cholesterol in the lysosomal lumen. It works in conjunction with the NPC1 protein to transport cholesterol from the lysosome to other parts of the cell. This process is essential for maintaining cellular cholesterol homeostasis. NPC2 has a high affinity for unesterified cholesterol and is thought to transfer cholesterol to NPC1, which is embedded in the lysosomal membrane.

Clinical Significance

Mutations in the NPC2 gene can lead to Niemann-Pick disease, type C2, a rare, inherited neurodegenerative disorder characterized by the accumulation of cholesterol and other lipids in the lysosome. This accumulation leads to a variety of symptoms, including hepatosplenomegaly, ataxia, dystonia, and progressive neurological decline.

Structure

The NPC2 protein is composed of 151 amino acids and has a molecular weight of approximately 16.5 kDa. It contains a cholesterol-binding domain that is critical for its function. The structure of NPC2 has been resolved by X-ray crystallography, revealing a beta-sandwich fold that is typical of lipid-binding proteins.

Genetic Information

The NPC2 gene is located on chromosome 14q24.3. It consists of 5 exons and spans approximately 14 kb of genomic DNA. The gene is expressed in various tissues, with high levels in the liver, spleen, and brain.

Research and Therapeutic Approaches

Research into NPC2 and its role in cholesterol transport has led to a better understanding of lipid metabolism disorders. Therapeutic approaches for Niemann-Pick disease type C2 include substrate reduction therapy, cholesterol-lowering agents, and gene therapy. However, these treatments are still under investigation and are not yet widely available.

Also see

• Niemann-Pick disease
• Cholesterol metabolism
• Lysosomal storage disorders
• NPC1