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We used molecular docking to propose (a) that NPC1 exports not just cholesterol, but also sphingosine, (b) that the cholesterol sensitivity of big potassium channel (BK) can be traced to a previously unappreciated site on the channel\u2019s voltage sensor, (c) that transient receptor potential mucolipin 1 (TRPML1) inhibition by sphingomyelin is likely an indirect effect, and (d) that phosphoinositides are responsible for both the mislocalization of annexin A2 (AnxA2) and a soluble NSF (N-ethylmaleimide Sensitive Fusion) protein attachment receptor (SNARE) recycling defect. These results are set in the context of existing knowledge of NPCD to sketch an account of the endolysosomal pathology key to this disease.<\/jats:p>","DOI":"10.3390\/ijms20030717","type":"journal-article","created":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T11:50:33Z","timestamp":1549540233000},"page":"717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Lipid\u2013Protein Interactions in Niemann\u2013Pick Type C Disease: Insights from Molecular Modeling"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0215-8648","authenticated-orcid":false,"given":"Simon","family":"Wheeler","sequence":"first","affiliation":[{"name":"School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9BH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0203-4023","authenticated-orcid":false,"given":"Ralf","family":"Schmid","sequence":"additional","affiliation":[{"name":"Leicester Institute of Structural and Chemical Biology, Henry Wellcome Building, University of Leicester, Lancaster Road, Leicester LE1 7RH, UK"},{"name":"Department of Molecular and Cell Biology, Henry Wellcome Building, University of Leicester, Lancaster Road, Leicester LE1 7RH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4747-5655","authenticated-orcid":false,"given":"Dan J","family":"Sillence","sequence":"additional","affiliation":[{"name":"School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9BH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18932","DOI":"10.1073\/pnas.1110439108","article-title":"Niemann\u2013Pick Type C 1 Function Requires Lumenal Domain Residues That Mediate Cholesterol-Dependent NPC2 Binding","volume":"108","author":"Deffieu","year":"2011","journal-title":"Proc. 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