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Sphingolipids have indispensable functions as signaling molecules and are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Ceramide is the precursor for all sphingolipids, and here we report the identification, localization and analyses of the\n                    <jats:italic>Toxoplasma<\/jats:italic>\n                    ceramide synthases\n                    <jats:italic>Tg<\/jats:italic>\n                    CerS1 and\n                    <jats:italic>Tg<\/jats:italic>\n                    CerS2. Interestingly, we observed that while\n                    <jats:italic>Tg<\/jats:italic>\n                    CerS1 was a fully functional orthologue of the yeast ceramide synthase (Lag1p) capable of catalyzing the conversion of sphinganine to ceramide, in contrast\n                    <jats:italic>Tg<\/jats:italic>\n                    CerS2 was catalytically inactive. Furthermore, genomic deletion of\n                    <jats:italic>Tg<\/jats:italic>\n                    CerS1 using CRISPR\/Cas\u20109 led to viable but slow\u2010growing parasites indicating its importance but not indispensability. In contrast, genomic knock out of\n                    <jats:italic>Tg<\/jats:italic>\n                    CerS2 was only accessible utilizing the rapamycin\u2010inducible Cre recombinase system. Surprisingly, the results demonstrated that this \u201cpseudo\u201d ceramide synthase,\n                    <jats:italic>Tg<\/jats:italic>\n                    CerS2, has a considerably greater role in parasite fitness than its catalytically active orthologue (\n                    <jats:italic>Tg<\/jats:italic>\n                    CerS1). Phylogenetic analyses indicated that, as in humans and plants, the ceramide synthase isoforms found in\n                    <jats:italic>Toxoplasma<\/jats:italic>\n                    and other Apicomplexa may have arisen through gene duplication. However, in the Apicomplexa the duplicated copy is hypothesized to have subsequently evolved into a non\u2010functional \u201cpseudo\u201d ceramide synthase. This arrangement is unique to the Apicomplexa and further illustrates the unusual biology that characterize these protozoan parasites.\n                  <\/jats:p>","DOI":"10.1096\/fj.202201603rrr","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T16:03:40Z","timestamp":1696521820000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<i>Toxoplasma<\/i>\n                    ceramide synthases: Gene duplication, functional divergence, and roles in parasite fitness"],"prefix":"10.1096","volume":"37","author":[{"given":"Zisis","family":"Koutsogiannis","sequence":"first","affiliation":[{"name":"Department of Biosciences Durham University  Durham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0429-1370","authenticated-orcid":false,"given":"John G.","family":"Mina","sequence":"additional","affiliation":[{"name":"Department of Biosciences Durham University  Durham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6259-7151","authenticated-orcid":false,"given":"Christin A.","family":"Albus","sequence":"additional","affiliation":[{"name":"Department of Biosciences Durham University  Durham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3068-6501","authenticated-orcid":false,"given":"Matthijs A.","family":"Kol","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology Division, Department of Biology\/Chemistry University of Osnabr\u00fcck  Osnabr\u00fcck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8912-1586","authenticated-orcid":false,"given":"Joost\u00a0C. 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