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Although individually very rare, they occur at a collective frequency of approximately one in five thousand live births and usually have catastrophic consequences for health. The lysosomal storage diseases Niemann\u2010Pick disease type C (<jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>) is caused by mutations predominantly in the lysosomal integral membrane protein <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>1 and clinically presents as a progressive neurodegenerative disorder. In this article we review data that demonstrate significant dysregulation of innate immunity in <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>, which occurs both in peripheral organs and the CNS. In particular pro\u2010inflammatory responses promote disease progression and anti\u2010inflammatory drugs provide benefit in animal models of the disease and are an attractive target for clinical intervention in this disorder.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13138-fig-0004-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Niemann\u2010Pick disease type C is a rare, devastating, inherited lysosomal storage disease with a unique cellular phenotype characterized by lysosomal accumulation of sphingosine, various glycosphingolipids and cholesterol and a reduction in lysosomal calcium. In this review we highlight the impact of the disease on innate immune activities in both the central nervous system (CNS) and peripheral tissues and discuss their contributions to pathology and the underlying mechanisms.<\/jats:p>","DOI":"10.1111\/jnc.13138","type":"journal-article","created":{"date-parts":[[2015,5,6]],"date-time":"2015-05-06T16:16:41Z","timestamp":1430929001000},"page":"74-80","source":"Crossref","is-referenced-by-count":65,"title":["Immune dysfunction in Niemann\u2010Pick disease type C"],"prefix":"10.1111","volume":"136","author":[{"given":"Nick","family":"Platt","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelise O.","family":"Speak","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandria","family":"Colaco","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerri\u2010Lee","family":"Wallom","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances M.","family":"Platt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,4]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/35094583"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.12.001"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00345-5"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9075-9"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141711"},{"key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"875","DOI":"10.3233\/JAD-2012-120199","article-title":"Niemann\u2010Pick C1 mice, a model of \u201cjuvenile Alzheimer's disease\u201d, with normal gene expression in neurons and fibrillary astrocytes show long term survival and delayed neurodegeneration","volume":"30","author":"Borbon I.","year":"2012","journal-title":"J. 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