{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:08:40Z","timestamp":1790662120363,"version":"4.1.0"},"reference-count":186,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,19]],"date-time":"2020-09-19T00:00:00Z","timestamp":1600473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009056","name":"Canadian Glycomics Network","doi-asserted-by":"publisher","award":["ND-03"],"award-info":[{"award-number":["ND-03"]}],"id":[{"id":"10.13039\/501100009056","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glycosphingolipids (GSLs) are a specialized class of membrane lipids composed of a ceramide backbone and a carbohydrate-rich head group. GSLs populate lipid rafts of the cell membrane of eukaryotic cells, and serve important cellular functions including control of cell\u2013cell signaling, signal transduction and cell recognition. Of the hundreds of unique GSL structures, anionic gangliosides are the most heavily implicated in the pathogenesis of lysosomal storage diseases (LSDs) such as Tay-Sachs and Sandhoff disease. Each LSD is characterized by the accumulation of GSLs in the lysosomes of neurons, which negatively interact with other intracellular molecules to culminate in cell death. In this review, we summarize the biosynthesis and degradation pathways of GSLs, discuss how aberrant GSL metabolism contributes to key features of LSD pathophysiology, draw parallels between LSDs and neurodegenerative proteinopathies such as Alzheimer\u2019s and Parkinson\u2019s disease and lastly, discuss possible therapies for patients.<\/jats:p>","DOI":"10.3390\/ijms21186881","type":"journal-article","created":{"date-parts":[[2020,9,19]],"date-time":"2020-09-19T07:06:09Z","timestamp":1600499169000},"page":"6881","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Metabolism of Glycosphingolipids and Their Role in the Pathophysiology of Lysosomal Storage Disorders"],"prefix":"10.3390","volume":"21","author":[{"given":"Alex E.","family":"Ryckman","sequence":"first","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, ON K7L 2V5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inka","family":"Brockhausen","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, ON K7L 2V5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagdeep S.","family":"Walia","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, ON K7L 2V5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"jcs219204","DOI":"10.1242\/jcs.219204","article-title":"Glycosphingolipid metabolism in cell fate specification","volume":"131","author":"Russo","year":"2018","journal-title":"J. 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