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Niemann-Pick disease type C (NPC) is a fatal neurodegenerative disorder characterised by accumulation of free cholesterol and glycosphingolipids in the late endosome (LE) and lysosome (Ly). Loss-of-function mutations in the NPC1 gene account for as high as 95% incidence among all NPC cases. The large transmembrane glycoprotein NPC1 comprises 3 large luminal loops, 13 transmembrane domains, and 6 cytosolic loops. While the luminal loops appear to be critical in interacting with NPC2 and transferring low density lipoprotein (LDL)-derived cholesterol to NPC1, the roles of the 6 cytosolic loops are unknown. Here, a series of NPC1 constructs lacking cytosolic loops were made, and their expression and ability to transport cholesterol were investigated by western blotting and filipin staining. All 6 loops except the second one are required for the expression and/or proper function of NPC1. To further understand the molecular function of NPC1, the interaction between NPC1 and SLP-1 was investigated as both are lipid/cholesterol binding proteins that localize to late endosomes and lysosomes. NPC1 appears to co-localize and co-immuoprecipitate with SLP-1. Overall, the results from this project provided some important insights into the regulation and function of NPC1.