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Protein disulfide isomerases (PDIs) are ER-resident enzymes that facilitate the formation, breakage, and rearrangement of disulfide bonds between cysteine residues, thereby stabilizing protein structures. Although PDIs are functionally diverse, they all contain at least 1 thioredoxin-like domain and most mediate disulfide exchange through their conserved CXXC motifs. The apicomplexan parasite,\n                      <jats:italic toggle=\"yes\">Toxoplasma gondii<\/jats:italic>\n                      , infects approximately one-third of the world population, posing a significant risk to immunosuppressed individuals and unborn fetuses. The fast-replicating tachyzoite form engages in a lytic cycle, causing host tissue damage and contributing to pathogenesis. While approximately 26 PDIs are predicted to be present in\n                      <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                      , their specific roles remain largely unexplored. In this study, we investigate TgPDIA3, a\n                      <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                      PDI localized to the ER, along with several of its interacting protein substrates. We explore its role in ER redox activity and calcium sequestration and assess how these functions contribute to the parasite\u2019s lytic cycle.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The lytic cycle of\n                        <jats:italic toggle=\"yes\">Toxoplasma gondii<\/jats:italic>\n                        is critical for parasite dissemination and disease progression in the host. Calcium signaling plays a crucial role in driving these processes; however, the molecules that control calcium storage and release remain poorly understood. The endoplasmic reticulum, likely the largest calcium reservoir in\n                        <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                        , has been understudied in the context of calcium signaling. Here, we uncover a direct link between ER redox regulation and calcium homeostasis, showing that ER redox activity can influence calcium signaling events that govern microneme protein maturation and secretion, parasite invasion, and replication. Our findings indicate that redox-dependent calcium regulation in the ER contributes to control of the parasite lytic cycle and reveals a previously unrecognized mechanism that may influence parasite virulence.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03124-25","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T13:01:24Z","timestamp":1775048484000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["A protein disulfide isomerase coordinates redox homeostasis and ER calcium regulation for optimal lytic cycle progression in\n                    <i>Toxoplasma gondii<\/i>"],"prefix":"10.1128","volume":"17","author":[{"given":"Katherine E.","family":"Moen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00te3t702","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Tropical and Emerging Global Diseases, University of Georgia","place":["Athens, USA"]},{"id":[{"id":"https:\/\/ror.org\/00te3t702","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cellular Biology, University of Georgia","place":["Athens, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2041-6295","authenticated-orcid":true,"given":"Silvia N. 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