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The appearance of resistance to first line artemisinin\u2010based therapies emphasizes the need to identify new parasite vulnerabilities to develop new therapeutics. Phosphoinositides are central regulators of membrane identity, vesicular trafficking, and signaling, and their synthesis depends on tightly controlled phosphatidylinositol transfer by Sec14\u2010like phosphatidylinositol transfer proteins in many eukaryotes, yet their roles in\n                    <jats:italic>P.\u2009falciparum<\/jats:italic>\n                    remain poorly defined. Here, we analyzed six\n                    <jats:italic>P.\u2009falciparum<\/jats:italic>\n                    Sec14 domain\u2013containing proteins: PfSec14\u20101 (PF3D7_0626400), PfSec14\u20102 (PF3D7_0629900), PfSec14\u20103 (PF3D7_0717100), PfSec14\u20104 (PF3D7_0920700), PfSec14\u20105 (PF3D7_1007200), and PfSec14\u20106 (PF3D7_1127600). Domain organization segregates these proteins into a BNIP\u20102 and Cdc42GAP homology (BCH) subfamily (PfSec14\u20103, PfSec14\u20105) and a canonical Sec14 subfamily (PfSec14\u20101, PfSec14\u20102, PfSec14\u20104, and PfSec14\u20106). Yeast complementation assays showed that PfSec14\u20101, PfSec14\u20104, and PfSec14\u20106 partially rescue growth of a temperature\u2010sensitive sec14 mutant, suggesting phosphatidylinositol and phosphatidylcholine transfer activity. Gene disruption revealed that PfSec14\u20101 is important for asexual blood\u2010stage proliferation, whereas PfSec14\u20102 is dispensable under standard culture conditions. In contrast, mislocalization of PfSec14\u20102 and PfSec14\u20104 using a knock\u2010sideways approach did not impair asexual growth. Subcellular localization indicates distinct distributions for PfSec14\u20101, PfSec14\u20102, and PfSec14\u20104. Together, these findings reveal potential functional and spatial diversification of Sec14\u2010like phosphatidylinositol transfer proteins in\n                    <jats:italic>P.\u2009falciparum<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/mmi.70107","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:14:11Z","timestamp":1786608851000},"page":"412-432","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of Sec14 Domain\u2013Containing Proteins in the Malaria Parasite\n                    <i>Plasmodium falciparum<\/i>"],"prefix":"10.1111","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5919-1372","authenticated-orcid":false,"given":"Florian","family":"Lauruol","sequence":"first","affiliation":[{"name":"Department of Microbiology\u2010Infectious Diseases and Immunology, Faculty of Medicine Universit\u00e9 Laval  Qu\u00e9bec Quebec Canada"},{"name":"CHU de Qu\u00e9bec\u2010Universit\u00e9 Laval Research Centre  Qu\u00e9bec Quebec Canada"},{"name":"Centre de Recherche en Infectiologie de l'Universit\u00e9 Laval  Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2015-4309","authenticated-orcid":false,"given":"Dominik","family":"\u0160\u0165astn\u00fd","sequence":"additional","affiliation":[{"name":"Centre of Biosciences, Institute of Animal Biochemistry and Genetics Slovak Academy of Sciences  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9921-5487","authenticated-orcid":false,"given":"J. Pedro","family":"Fernandez\u2010Murray","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0822-5776","authenticated-orcid":false,"given":"Christopher R.","family":"McMaster","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3538-0405","authenticated-orcid":false,"given":"Peter","family":"Gria\u010d","sequence":"additional","affiliation":[{"name":"Centre of Biosciences, Institute of Animal Biochemistry and Genetics Slovak Academy of Sciences  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2269-6240","authenticated-orcid":false,"given":"Dave","family":"Richard","sequence":"additional","affiliation":[{"name":"Department of Microbiology\u2010Infectious Diseases and Immunology, Faculty of Medicine Universit\u00e9 Laval  Qu\u00e9bec Quebec Canada"},{"name":"CHU de Qu\u00e9bec\u2010Universit\u00e9 Laval Research Centre  Qu\u00e9bec Quebec Canada"},{"name":"Centre de Recherche en Infectiologie de l'Universit\u00e9 Laval  Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007487\u2010w"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11449"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201001397\u20101"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2022.101146"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.108.4.1271"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2009.10.008"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/157.3.1117"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4223"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.1.389"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.24552"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1082"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001806"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.06.030"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20092167"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01507\u201023"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864\u2010020\u201006787\u20105"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102861"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2014242118"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092\u20108674(91)90508\u2010v"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12206"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky354"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e02\u201012\u20100830"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2017.08.015"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/14.9.755"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201034630\u2010w"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb01036.x"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6042"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10727"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R089730"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.08.003"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033863"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0138626"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2019.12.007"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2014.07.014"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb\u20102001\u20102\u20109\u2010reviews3011"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2016.03.027"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.11005.1"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20210281"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E07\u201001\u20100040"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep21800"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12236"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44318\u2010024\u201000096\u20103"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201003984\u20103"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936\u2010020\u201003436\u2010w"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201017505\u20109"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2018.12.239"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2024.10.018"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbior.2020.100740"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115993"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2023.159365"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00663"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.56773"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12782"},{"key":"e_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