{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T18:19:16Z","timestamp":1787681956698,"version":"build-2784847793"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM146584"],"award-info":[{"award-number":["P20GM146584"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    As a eukaryote,\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    , the causative agent of malaria, is reliant on its endoplasmic reticulum (ER) for survival. However, as a protozoan pathogen,\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    has also adapted its ER to support its parasitic lifestyle. This Pearl focuses on the interplay between conserved ER functions in\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    such as cell signaling, protein synthesis\/secretion, lipid production, and cellular stress, and their contribution to parasite pathogenesis. We further summarize the current knowledge about the role of the ER in pathogenic processes such as motility, egress\/invasion, host-cell remodeling, and transmission throughout the blood, liver, sexual, and mosquito stages. Collectively, we hope that discussing the\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    ER as both a conserved cellular hub and a source of parasite-specific biology offers promising opportunities for antimalarial strategies.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014539","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T17:28:13Z","timestamp":1787678893000},"page":"e1014539","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["The long and winding road: On the endoplasmic reticulum of Plasmodium and implications for pathogenesis"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7642-6241","authenticated-orcid":true,"given":"Antonia","family":"Blank","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon","family":"Ngwira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8729-5945","authenticated-orcid":true,"given":"Manuel A.","family":"Fierro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"issue":"2","key":"ppat.1014539.ref001","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1534\/genetics.112.142810","article-title":"Secretory protein biogenesis and traffic in the early secretory pathway","volume":"193","author":"CK Barlowe","year":"2013","journal-title":"Genetics"},{"issue":"1","key":"ppat.1014539.ref002","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a041250","article-title":"Mechanism of protein translocation by the Sec61 translocon complex","volume":"15","author":"S Itskanov","year":"2023","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"7","key":"ppat.1014539.ref003","doi-asserted-by":"crossref","first-page":"102061","DOI":"10.1016\/j.jbc.2022.102061","article-title":"Regulation of calcium homeostasis and flux between the endoplasmic reticulum and the cytosol","volume":"298","author":"L Daverkausen-Fischer","year":"2022","journal-title":"J Biol Chem"},{"issue":"1","key":"ppat.1014539.ref004","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/s41392-023-01570-w","article-title":"Endoplasmic reticulum stress: molecular mechanism and therapeutic targets","volume":"8","author":"X Chen","year":"2023","journal-title":"Signal Transduct Target Ther"},{"issue":"9","key":"ppat.1014539.ref005","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0076278","article-title":"Comparative genomic analysis of multi-subunit tethering complexes demonstrates an ancient pan-eukaryotic complement and sculpting in Apicomplexa","volume":"8","author":"CM Klinger","year":"2013","journal-title":"PLoS One"},{"key":"ppat.1014539.ref006","article-title":"Chromerid genomes reveal the evolutionary path from photosynthetic algae to obligate intracellular parasites","volume":"4","author":"YH Woo","year":"2015","journal-title":"Elife"},{"key":"ppat.1014539.ref007","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.molbiopara.2016.07.003","article-title":"Resolving the homology-function relationship through comparative genomics of membrane-trafficking machinery and parasite cell biology","volume":"209","author":"CM Klinger","year":"2016","journal-title":"Mol Biochem Parasitol"},{"key":"ppat.1014539.ref008","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.03078-19","article-title":"An endoplasmic reticulum CREC family protein regulates the egress proteolytic cascade in malaria parasites","volume":"11","author":"MA Fierro","year":"2020","journal-title":"mBio"},{"issue":"2","key":"ppat.1014539.ref009","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.pt.2023.12.006","article-title":"Glycosylation in malaria parasites: what do we know?","volume":"40","author":"DC Gowda","year":"2024","journal-title":"Trends Parasitol"},{"issue":"24","key":"ppat.1014539.ref010","doi-asserted-by":"crossref","first-page":"16662","DOI":"10.1074\/jbc.M114.551549","article-title":"Endoplasmic reticulum stress triggers gametocytogenesis in the malaria parasite","volume":"289","author":"S Chaubey","year":"2014","journal-title":"J Biol Chem"},{"issue":"9","key":"ppat.1014539.ref011","first-page":"937","article-title":"Protein sorting in Plasmodium falciparum","volume":"11","author":"DCG Mayer","year":"2021","journal-title":"Life (Basel)"},{"issue":"6","key":"ppat.1014539.ref012","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a041259","article-title":"Structural diversity within the endoplasmic reticulum-from the microscale to the nanoscale","volume":"15","author":"CJ Obara","year":"2023","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"3","key":"ppat.1014539.ref013","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1111\/mmi.14526","article-title":"A Plasmodium homolog of ER tubule-forming proteins is required for parasite virulence","volume":"114","author":"X Shi","year":"2020","journal-title":"Mol Microbiol"},{"issue":"8","key":"ppat.1014539.ref014","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s13238-016-0290-5","article-title":"Identification of endoplasmic reticulum-shaping proteins in Plasmodium parasites","volume":"7","author":"S Sun","year":"2016","journal-title":"Protein Cell"},{"issue":"2","key":"ppat.1014539.ref015","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/j.1365-2958.2005.04699.x","article-title":"Development of the endoplasmic reticulum, mitochondrion and apicoplast during the asexual life cycle of Plasmodium falciparum","volume":"57","author":"GG van Dooren","year":"2005","journal-title":"Mol Microbiol"},{"key":"ppat.1014539.ref016","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.mito.2022.05.005","article-title":"Defining ER-mitochondria contact dynamics in Plasmodium falciparum by targeting component of phospholipid synthesis pathway, phosphatidylserine synthase (PfPSS)","volume":"65","author":"MO Anwar","year":"2022","journal-title":"Mitochondrion"},{"key":"ppat.1014539.ref017","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.88088.3","article-title":"Atlas of Plasmodium falciparum intraerythrocytic development using expansion microscopy","volume":"12","author":"B Liffner","year":"2023","journal-title":"Elife"},{"issue":"5","key":"ppat.1014539.ref018","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1111\/mmi.13490","article-title":"High resolution microscopy reveals an unusual architecture of the Plasmodium berghei endoplasmic reticulum","volume":"102","author":"G Kaiser","year":"2016","journal-title":"Mol Microbiol"},{"issue":"1","key":"ppat.1014539.ref019","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41467-024-55413-5","article-title":"Comparative 3D ultrastructure of Plasmodium falciparum gametocytes","volume":"16","author":"F Evers","year":"2025","journal-title":"Nat Commun"},{"issue":"3","key":"ppat.1014539.ref020","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1011210","article-title":"Same, same but different: exploring Plasmodium cell division during liver stage development","volume":"19","author":"M Roques","year":"2023","journal-title":"PLoS Pathog"},{"key":"ppat.1014539.ref021","doi-asserted-by":"crossref","first-page":"708834","DOI":"10.3389\/fcimb.2021.708834","article-title":"Calcium in the backstage of malaria parasite biology","volume":"11","author":"LS de Oliveira","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"issue":"7","key":"ppat.1014539.ref022","doi-asserted-by":"crossref","DOI":"10.1111\/cmi.13215","article-title":"Directing traffic: chaperone-mediated protein transport in malaria parasites","volume":"22","author":"A Florentin","year":"2020","journal-title":"Cell Microbiol"},{"issue":"13","key":"ppat.1014539.ref023","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abe5396","article-title":"Ca2+ signals critical for egress and gametogenesis in malaria parasites depend on a multipass membrane protein that interacts with PKG","volume":"7","author":"AC Balestra","year":"2021","journal-title":"Sci Adv"},{"issue":"2","key":"ppat.1014539.ref024","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41579-025-01235-1","article-title":"Erythrocyte invasion in malaria: from molecular mechanisms to rational vaccines","volume":"24","author":"N Alam","year":"2026","journal-title":"Nat Rev Microbiol"},{"key":"ppat.1014539.ref025","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1146\/annurev-micro-041320-020659","article-title":"Plasmodium egress across the parasite life cycle","volume":"76","author":"JD Dvorin","year":"2022","journal-title":"Annu Rev Microbiol"},{"issue":"33","key":"ppat.1014539.ref026","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2308676120","article-title":"Knock-sideways by inducible ER retrieval enables a unique approach for studying Plasmodium-secreted proteins","volume":"120","author":"MA Fierro","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ppat.1014539.ref027","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1038\/s41467-020-15440-4","article-title":"Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway","volume":"11","author":"GM LaMonte","year":"2020","journal-title":"Nat Commun"},{"key":"ppat.1014539.ref028","doi-asserted-by":"crossref","first-page":"21486","DOI":"10.1073\/pnas.1216016110","article-title":"Targeting the ERAD pathway via inhibition of signal peptide peptidase for antiparasitic therapeutic design","volume":"109","author":"MB Harbut","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"ppat.1014539.ref029","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003426","article-title":"An apicoplast localized ubiquitylation system is required for the import of nuclear-encoded plastid proteins","volume":"9","author":"S Agrawal","year":"2013","journal-title":"PLoS Pathog"},{"issue":"5703","key":"ppat.1014539.ref030","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1126\/science.1102452","article-title":"Targeting malaria virulence and remodeling proteins to the host erythrocyte","volume":"306","author":"M Marti","year":"2004","journal-title":"Science"},{"issue":"5703","key":"ppat.1014539.ref031","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1126\/science.1102737","article-title":"A host-targeting signal in virulence proteins reveals a secretome in malarial infection","volume":"306","author":"NL Hiller","year":"2004","journal-title":"Science"},{"issue":"9","key":"ppat.1014539.ref032","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1038\/s41564-018-0219-2","article-title":"Plasmepsin V cleaves malaria effector proteins in a distinct endoplasmic reticulum translocation interactome for export to the erythrocyte","volume":"3","author":"DS Marapana","year":"2018","journal-title":"Nat Microbiol"},{"issue":"2","key":"ppat.1014539.ref033","doi-asserted-by":"crossref","DOI":"10.1128\/msphere.00393-23","article-title":"PEXEL is a proteolytic maturation site for both exported and non-exported Plasmodium proteins","volume":"9","author":"MA Fierro","year":"2024","journal-title":"mSphere"},{"issue":"4","key":"ppat.1014539.ref034","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1021\/acsinfecdis.9b00460","article-title":"Assessment of biological role and insight into druggability of the Plasmodium falciparum protease plasmepsin V","volume":"6","author":"AJ Polino","year":"2020","journal-title":"ACS Infect Dis"},{"issue":"8","key":"ppat.1014539.ref035","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/nsmb.3061","article-title":"Structural basis for plasmepsin V inhibition that blocks export of malaria proteins to human erythrocytes","volume":"22","author":"AN Hodder","year":"2015","journal-title":"Nat Struct Mol Biol"},{"issue":"2","key":"ppat.1014539.ref036","article-title":"A redox-active crosslinker reveals an essential and inhibitable oxidative folding network in the endoplasmic reticulum of malaria parasites","volume":"17","author":"DW Cobb","year":"2021","journal-title":"PLoS Pathog"},{"key":"ppat.1014539.ref037","doi-asserted-by":"crossref","first-page":"712538","DOI":"10.3389\/fmicb.2021.712538","article-title":"Unveiling the sugary secrets of Plasmodium parasites","volume":"12","author":"F Goerdeler","year":"2021","journal-title":"Front Microbiol"},{"key":"ppat.1014539.ref038","doi-asserted-by":"crossref","first-page":"108178","DOI":"10.1016\/j.biotechadv.2023.108178","article-title":"The glycobiology of Plasmodium falciparum: new approaches and recent advances","volume":"66","author":"L Izquierdo","year":"2023","journal-title":"Biotechnol Adv"},{"issue":"8","key":"ppat.1014539.ref039","doi-asserted-by":"crossref","first-page":"107557","DOI":"10.1016\/j.jbc.2024.107557","article-title":"The major surface protein of malaria sporozoites is GPI-anchored to the plasma membrane","volume":"300","author":"R Nagar","year":"2024","journal-title":"J Biol Chem"},{"issue":"1","key":"ppat.1014539.ref040","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/s41467-017-00571-y","article-title":"Protein O-fucosylation in Plasmodium falciparum ensures efficient infection of mosquito and vertebrate hosts","volume":"8","author":"S Lopaticki","year":"2017","journal-title":"Nat Commun"},{"issue":"1","key":"ppat.1014539.ref041","doi-asserted-by":"crossref","first-page":"4400","DOI":"10.1038\/s41467-022-32076-8","article-title":"Tryptophan C-mannosylation is critical for Plasmodium falciparum transmission","volume":"13","author":"S Lopaticki","year":"2022","journal-title":"Nat Commun"},{"key":"ppat.1014539.ref042","doi-asserted-by":"crossref","first-page":"158492","DOI":"10.1016\/j.bbalip.2019.07.001","article-title":"Specialized ER membrane domains for lipid metabolism and transport","volume":"1865","author":"T Nishimura","year":"2020","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"issue":"45","key":"ppat.1014539.ref043","doi-asserted-by":"crossref","first-page":"17308","DOI":"10.1074\/jbc.R118.003213","article-title":"Role of phospholipid synthesis in the development and differentiation of malaria parasites in the blood","volume":"293","author":"N Kilian","year":"2018","journal-title":"J Biol Chem"},{"issue":"1","key":"ppat.1014539.ref044","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1038\/s41467-026-70887-1","article-title":"A bridge-like lipid transfer protein is critical for generation of invasive stages in malaria parasites","volume":"17","author":"A Guill\u00e9n-Samander","year":"2026","journal-title":"Nat Commun"},{"issue":"20","key":"ppat.1014539.ref045","article-title":"Lipid droplet dynamics are essential for the development of the malaria parasite Plasmodium falciparum","volume":"137","author":"J Lee","year":"2024","journal-title":"J Cell Sci"},{"key":"ppat.1014539.ref046","article-title":"Lysophosphatidylcholine regulates sexual stage differentiation in the human malaria parasite Plasmodium falciparum","volume":"171","author":"NMB Brancucci","year":"2017","journal-title":"Cell"},{"key":"ppat.1014539.ref047","doi-asserted-by":"crossref","first-page":"148742","DOI":"10.1016\/j.brainres.2023.148742","article-title":"Endoplasmic reticulum stress and its role in various neurodegenerative diseases","volume":"1826","author":"R Singh","year":"2024","journal-title":"Brain Res"},{"key":"ppat.1014539.ref048","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s10930-025-10264-x","article-title":"Endoplasmic reticulum Stress: implications in diseases","volume":"44","author":"NS Walter","year":"2025","journal-title":"The Protein Journal"},{"issue":"6","key":"ppat.1014539.ref049","doi-asserted-by":"crossref","DOI":"10.1016\/j.chom.2017.11.005","article-title":"Inhibiting the Plasmodium eIF2\u03b1 kinase PK4 prevents artemisinin-induced latency","volume":"22","author":"M Zhang","year":"2017","journal-title":"Cell Host Microbe"},{"issue":"2","key":"ppat.1014539.ref050","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1128\/EC.00296-12","article-title":"Translational control in Plasmodium and toxoplasma parasites","volume":"12","author":"M Zhang","year":"2013","journal-title":"Eukaryot Cell"},{"issue":"6220","key":"ppat.1014539.ref051","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1126\/science.1260403","article-title":"Drug resistance. Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance","volume":"347","author":"S Mok","year":"2015","journal-title":"Science"},{"issue":"9","key":"ppat.1014539.ref052","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2005895","article-title":"Integrative proteomics and bioinformatic prediction enable a high-confidence apicoplast proteome in malaria parasites","volume":"16","author":"MJ Boucher","year":"2018","journal-title":"PLoS Biol"},{"issue":"1","key":"ppat.1014539.ref053","doi-asserted-by":"crossref","first-page":"6192","DOI":"10.1038\/s41467-026-73664-2","article-title":"The spatial proteome of the Plasmodium falciparum schizont illuminates the composition and evolutionary trajectories of its organelles","volume":"17","author":"SA Chisholm","year":"2026","journal-title":"Nat Commun"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014539","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T17:28:20Z","timestamp":1787678900000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014539"}},"subtitle":[],"editor":[{"given":"Tobias","family":"Spielmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,25]]},"references-count":53,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1014539","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,25]]}}}