{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:17:23Z","timestamp":1787919443762,"version":"build-2784847793"},"reference-count":68,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioEssays"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In humans, the\n                    <jats:italic>FLOWER<\/jats:italic>\n                    (\n                    <jats:italic>FWE<\/jats:italic>\n                    or\n                    <jats:italic>CACFD1<\/jats:italic>\n                    ) gene encodes a set of small, alternatively spliced transmembrane protein isoforms (hFWE1\u20104). The canonical human isoform, hFWE4, and its various orthologues, which we collectively refer to as FWE for simplicity, assumes a four transmembrane pass structure with cytosolic N\u2010 and C\u2010termini. This topology exposes YXX\u03a6 motifs enabling interaction with trafficking machinery and positions highly\u2010conserved cationic residues for interaction with membrane phospholipids. While identified initially as a mediator of synaptic vesicle endocytosis in presynaptic neurons, FWE is now recognized as a critical mediator of endo\u2010lysosome related organelle (ELRO) trafficking across diverse cell types including cytotoxic T\u2010lymphocytes and epidermal keratinocytes. A unifying feature of FWE function appears to be elevation of cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    levels. However, the underlying molecular mechanisms remain elusive. This review synthesizes current literature on FWE\u2010mediated membrane trafficking, highlighting the evolutionary conservation of its coding sequence and tertiary structure. We propose new structure\u2010compatible hypotheses for FWE\u2010dependent cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    elevation and subsequent ELRO trafficking, highlighting experimental strategies that may aid testing of these hypotheses. Finally, we examine the distinct localizations and potential functions of non\u2010canonical FWE isoforms.\n                  <\/jats:p>","DOI":"10.1002\/bies.70167","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T09:50:25Z","timestamp":1786614625000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Flower Delivery: The Emergence of FLOWER (FWE) as a Multifunctional Regulator of Endo\u2010Lysosome\u2010Related Organelle Trafficking Across Cell Types"],"prefix":"10.1002","volume":"48","author":[{"given":"Justin C.","family":"Rudd","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Creighton University  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Creighton University  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2019.05.003"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12646"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e05\u201007\u20100626"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e06\u201002\u20100103"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E11\u201006\u20100509"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201410026"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300090200"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E13\u201009\u20100521"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102013\u201010\u2010535831"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102008\u201006\u2010165282"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102007\u201007\u2010099309"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.221952"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.86556"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100854.2004.00257.x"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523\u20101747.2003.12367.x"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.5555\/uri:pii:0022202X94904170"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.05.010"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.008623"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.104945"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010024\u201002453\u20103"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12773"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2006.11.008"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.17.7696\u20107710.2005"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.06.033"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60125"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2001.111.re19"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092\u20108674(00)80696\u20100"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/312315a0"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.103870"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.222992"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201706053"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010024\u201005528\u20101"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1101\/2022.07.21.500999"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2012.02.017"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2020.05.009"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005645"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4697\u201012.2013"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.04.011"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2000931"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100854.2007.00547.x"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.08.016"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201002027"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600828"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201411093"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.22.6011"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092\u20108674(94)90442\u20101"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102133.2010.10046.x"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2025.05.024"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700850"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.02.001"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.12.021"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201062105\u20101"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xj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