The characteristics and biological significance of NPC2: Mutation and disease.

Niemann-Pick C disease (NPC) is a rare autosomal recessive disorder characterized by severe neurodegeneration of central nervous system. Linkage studies in multiplex NPC families and genetic complementation research revealed two disease genes, NPC1 and NPC2, both of which are important transporters for cholesterol trafficking. NPC2 executes cholesterol-transport function through protein-protein interaction with NPC1 as well as through protein-membrane interaction directly with membrane of late endosome and lysosome. In addition, NPC2 may play many other roles as indicated by its widely expressing pattern in different cells and presenting in numerous secretory fluids, although it biological significance is less studied today. About 50 clinical cases have been reported documenting over twenty different mutations of NPC2 in NPC patients so far. In this review, we will mainly summarize the molecular characteristics and biological significance of NPC2, highlighting its vital roles in NPC disease.