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This provides a direct molecular link between altered lipid abundance and myelin stability. We show that the NFASC isoform NF155, but not NF186, interacts directly and specifically with the sphingolipid sulfatide via multiple binding sites and that this interaction requires the full-length extracellular domain of NF155. We demonstrate that NF155 adopts an S-shaped conformation and preferentially binds sulfatide-containing membranes in\n                    <jats:italic>cis<\/jats:italic>\n                    , with important implications for protein arrangement in the tight axon-myelin space. Our work links glycosphingolipid imbalances to disturbance of membrane protein abundance and demonstrates how this may be driven by direct protein\u2013lipid interactions, providing a mechanistic framework to understand the pathogenesis of galactosphingolipidoses.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2218823120","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T13:48:58Z","timestamp":1680184138000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":12,"title":["Altered plasma membrane abundance of the sulfatide-binding protein NF155 links glycosphingolipid imbalances to demyelination"],"prefix":"10.1073","volume":"120","author":[{"given":"Shannon J.","family":"McKie","sequence":"first","affiliation":[{"name":"Department of Clinical Neuroscience, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, 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