NPC intracellular cholesterol transporter 2 (NPC2) mRNA (NPC2)

NPC2 mRNA encodes the NPC intracellular cholesterol transporter 2, a soluble lysosomal protein essential for cholesterol egress from the endolysosomal system [1, 4]. Within the lysosome, NPC2 binds to the hydrophobic side chain of unesterified cholesterol and transfers it to the membrane-bound NPC1 protein, which then facilitates cholesterol transport across the lysosomal membrane into the cytosol [1, 5]. Mutations in the NPC2 gene result in Niemann-Pick disease type C2, a rare and fatal lysosomal storage disorder characterized by the accumulation of cholesterol and other lipids in the liver, spleen, and brain [2, 5]. As a therapeutic target, NPC2 mRNA is utilized in mRNA replacement therapies, such as Moderna's mRNA-1325, where synthetic mRNA is delivered via lipid nanoparticles to restore functional protein levels [3]. This approach is designed to correct the underlying biochemical defect, normalize lipid trafficking, and potentially treat the progressive neurovisceral symptoms associated with the disease [3, 4]. Citations: [1] UniProt P61916; [2] NCBI Gene 10577; [3] Moderna Pipeline; [4] Infante et al. (2008) PNAS; [5] Vanier (2010) OJRD.

Other names

HE1Epididymal secretory protein E1Niemann-Pick disease type C2 protein mRNA

mRNA replacement therapy: Delivery of synthetic mRNA to cells to produce functional NPC2 protein, restoring lysosomal cholesterol transport.