Niemann–Pick C disease: cholesterol handling gone awry

Abstract Niemann–Pick C disease (NPC) is a debilitating, recessive disorder in humans that causes unrelenting neurological deterioration and is complicated by the presence of lipid-laden foamy cells in the major organs of the body. NPC fibroblasts cultured with an excess of low density lipoprotein (LDL) abnormally sequester cholesterol in their lysosomes. Biochemical analyses of NPC cells suggest an impairment in the intracellular transport of cholesterol to post-lysosomal destinations occurs in NPC. The recent identification of the NPC gene, NPC1 , provides a definitive diagnosis of the disease and a means of studying this key component of intracellular cholesterol transport and homeostasis.