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. 2022 Oct 31;20:172. doi: 10.1186/s12964-022-00956-7

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — Sphingolipid metabolism in a summary. Ceramide is a key component of sphingolipid metabolism. Ceramide is made from the condensation of serine and palmitoyl-CoA in the endoplasmatic reticulum (ER) by serine palmitoyltransferase (SPT). After further reduction and acylation by a ceramide synthase (CERS1-6), dihydrosphingosine (dHSph) is produced, which is then desaturated to generate ceramide. Ceramide can be altered to galactosylceramide (GalCer) in the ER, although most ceramide change occurs at the Golgi in a manner that is dependent on their following use. Ceramide is used in the Golgi to produce sphingomyelin (SM) and glycosphingolipids in processes mediated by sphingomyelin synthase 1 (SMS1) and glycosphingolipid synthases (GCSs). SM and glycosphingolipids are delivered to the plasma membrane from the Golgi. By the actions of secretory and neutral sphingomyelinases, SM can be converted back to ceramide (sSMase and nSMase). Ceramide can then be converted to ceramide-1-phosphate (C1P), sphingosine-1-phosphate (S1P), or SM. By accessing the endolysosomal process, complex sphingolipids in the membrane can be utilized as a pool for ceramide recycling. Acid SMases (aSMase) and glycosidases (GCase) create ceramide, which can then be hydrolyzed into sphingosine and utilized in ceramide production or degraded by phosphorylation into S1P followed by degradation to hexadecenal and ethanolamine-1-phosphate (EA1P). Ceramide kinase (CERK) can phosphorylate ceramide in the Golgi, resulting in ceramide-1-phosphate (C1P)