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Toxoplasma gondii is arguably the most succesful parasite in Earth and a major cause of abortion and opportunistic infections in humans and livestock. Understanding the metabolic flexibility of this parasite is essential to comprehend its adaptability. Lipids are basic components of biological membranes. However, in the last decades non-customary roles for lipids beyond membrane biogenesis have been recognized. Here we report for the first time phosphatidylthreonine (PtdThr) as a major phospholipid in T. gondii and show its relationship with its archetypical analog, phosphatidylserine (PtdSer). We also identify a novel parasite enzyme (TgPTS), which diverged from the mainstream PtdSer-synthase family to produce this otherwise rare lipid. Genetic ablation of TgPTS not only abolished PtdThr synthesis, but also impaired severely the lytic cycle of T. gondii, particularly the egress but also the invasion into host cells without affecting the parasite replication. Our work indicates that, either a lower Ca2+ pool and/or a diminished Ca2+ mobilization from the parasite endoplasmic reticulum cause a reduced gliding motility, which underlies the observed phenotypes. Moreover, the mutant parasites lacking PtdThr (Δtgpts) are avirulent and exert full protection against both, acute and chronic toxoplasmosis in a murine model. These results highlight the importance of parasite lipids as therapeutic targets and of genetically-attenuated strains in the development of effective vaccines against coccidian parasites.