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Although a neurovisceral disorder, it is above all a neurodegenerative disease in the vast majority of patients. Not an enzyme deficiency, it is currently conceived as a lipid trafficking disorder. Impaired egress of cholesterol from the late endosomal\/lysosomal (LE\/L) compartment is a specific and key element of the pathogenesis, but other lipids, more specially sphingolipids, are also involved, and there are indications for further abnormalities. The full function of the NPC1 and NPC2 proteins is still unclear. This review provides a reappraisal of lipid storage and lysosomal enzymes activities in tissues\/cells from NPC patients and animal models. It summarizes the current knowledge on the NPC1 and NPC2 proteins and their function in transport of cholesterol within the late endosomal\u2010lysosomal compartment, with emphasis on differences between systemic organs and the brain; it also discusses regulation by membrane lipids of the NPC2\u2010mediated cholesterol trafficking, interplay between cholesterol and sphingomyelin, the metabolic origin of glycosphingolipids stored in brain, and the putative role of free sphingoid bases in pathogenesis. Brief mention is finally made of diseases affecting other genes that were very recently shown to impact the \u201cNPC pathway\u201d.<\/jats:p>","DOI":"10.1007\/s10545-014-9794-4","type":"journal-article","created":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T15:35:17Z","timestamp":1417448117000},"page":"187-199","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":237,"title":["Complex lipid trafficking in Niemann\u2010Pick disease type C"],"prefix":"10.1002","volume":"38","author":[{"given":"Marie T.","family":"Vanier","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U820 Universit\u00e9 Lyon\u20101 EA4611, Facult\u00e9 de M\u00e9decine Lyon\u2010Est 7 Rue G. 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