{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T23:06:50Z","timestamp":1776553610098,"version":"3.51.2"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["IRTG2290"],"award-info":[{"award-number":["IRTG2290"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Letters"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Transmission of\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    parasites to\n                    <jats:italic>Anopheles<\/jats:italic>\n                    mosquitoes relies on rapid activation of mature gametocytes in the midgut, triggered by a temperature drop and xanthurenic acid. In\n                    <jats:italic>Plasmodium yoelii<\/jats:italic>\n                    , the gametogenesis essential protein 1 (GEP1) was linked to xanthurenic acid (XA)\u2010dependent gamete activation. We characterized\n                    <jats:italic>GEP1<\/jats:italic>\n                    in\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    using CRISPR\u2010Cas9 to create\n                    <jats:italic>PfGEP1<\/jats:italic>\n                    loss\u2010of\u2010function lines. These lines failed to undergo male or female gametogenesis, even when stimulated by XA or a temperature drop. The defect persisted despite treatment with the phosphodiesterase inhibitor Zaprinast. Analysis of field samples revealed two GEP1 single\u2010nucleotide polymorphisms (V241L and S263P) in 12% and 20% of 49 cases. Our findings confirm GEP1's essential role in gamete activation, highlight an XA\u2010independent function, and support its potential as a transmission\u2010blocking target.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"box\" position=\"anchor\">\n                      <jats:caption>\n                        <jats:title>Impact statement<\/jats:title>\n                      <\/jats:caption>\n                      <jats:p>\n                        For sustainable malaria control, transmission\u2010blocking drug targets are urgently needed. Work in murine models showed that GEP1 is a candidate. We show complete block of life cycle progression of the human malarial parasite\n                        <jats:italic>Plasmodium falciparum<\/jats:italic>\n                        when GEP1 is deleted, warranting targeted drug development to achieve gamete\u2010free mosquito blood meals.\n                      <\/jats:p>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1002\/1873-3468.70184","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T06:25:01Z","timestamp":1760423101000},"page":"239-250","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>Plasmodium falciparum<\/i>\n                    gametogenesis essential protein 1 (\n                    <scp>GEP1<\/scp>\n                    ) is a transmission\u2010blocking target"],"prefix":"10.1002","volume":"600","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3436-5425","authenticated-orcid":false,"given":"Frederik","family":"Huppertz","sequence":"first","affiliation":[{"name":"Department of Molecular Parasitology, Institute of Biology Humboldt University  Berlin Germany"},{"name":"Research School of Biology The Australian National University  Canberra Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milagros Siebeck","family":"Caturelli","sequence":"additional","affiliation":[{"name":"Department of Molecular Parasitology, Institute of Biology Humboldt University  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina S.","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Department of Molecular Parasitology, Institute of Biology Humboldt University  Berlin Germany"},{"name":"Department of Infectious Diseases and Critical Care Medicine Charit\u00e9 \u2010 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