My general interest is in the field of nutritional and metabolic biochemistry with a focus on the transport and homeostasis of lipids. For several years I have investigated the Niemann-Pick C1 (NPC1) gene and protein. The NPC1 protein has a central role in regulating the transport of low density lipoprotein (LDL)-derived cholesterol and fatty acids from late endosomes to various cellular compartments, including the plasma membrane for efflux and formation of high density lipoproteins (HDL). It is well known that genetic variation of the NPC1 gene is responsible for a rare autosomal-recessive lipid storage disease characterized by liver dysfunction and progressive neurological degeneration. However, our studies have also demonstrated that genetic variation of the NPC1 gene is associated with disparate metabolic diseases (obesity, insulin resistance, diabetes mellitus) which have reached epidemic proportions worldwide.