{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:18:40Z","timestamp":1792790320208,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,28]]},"group-title":"Cell Biology","reference-count":88,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01EY015625"],"award-info":[{"award-number":["R01EY015625"]}]},{"name":"National Institutes of Health","award":["R01AR076241"],"award-info":[{"award-number":["R01AR076241"]}]},{"name":"National Institutes of Health","award":["1R01AR085585-01"],"award-info":[{"award-number":["1R01AR085585-01"]}]},{"name":"National Institutes of Health","award":["1R35GM161902-01"],"award-info":[{"award-number":["1R35GM161902-01"]}]},{"name":"LEO Foundation","award":["LF-OC-25-002553"],"award-info":[{"award-number":["LF-OC-25-002553"]}],"id":[{"id":"https:\/\/ror.org\/02rgsr590","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Penn Skin Biology and Diseases Resource-based Center","award":["P30-AR069589"],"award-info":[{"award-number":["P30-AR069589"]}]},{"name":"Children's Hospital of Philadelphia Research Institute","award":["GRT-00006135"],"award-info":[{"award-number":["GRT-00006135"]}],"id":[{"id":"https:\/\/ror.org\/01z7r7q48","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  We previously found that skin tone correlates with intronic polymorphisms influencing the expression of the Joubert Syndrome (JS) ciliopathy gene\n                  <jats:italic>TMEM138<\/jats:italic>\n                  , suggesting that primary cilia might regulate pigment production in skin melanocytes. Herein, we show that many ciliary proteins regulate basal pigmentation in wild-type mouse and human melanocytes by facilitating primary cilium-dependent Melanocortin-1 receptor signaling, and downstream activation of the Microphthalmia transcription factor and melanogenic gene expression. Additionally, we identify an extra-ciliary moonlighting role for TMEM138 and other JS proteins in endolysosomal organization required for the biogenesis of melanosomes, the pigment-producing lysosome-related organelle in melanocytes. Our results provide new mechanistic insights into the physiological regulation of pigmentation and suggest that JS-specific pathology might be mediated by ciliary-independent mechanisms.\n                <\/jats:p>","DOI":"10.64898\/2026.09.27.754807","type":"posted-content","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:05:25Z","timestamp":1790629525000},"source":"Crossref","is-referenced-by-count":0,"title":["Ciliary regulation of melanogenesis unveils moonlighting roles for Joubert Syndrome proteins"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5052-1144","authenticated-orcid":false,"given":"Brice","family":"Magne","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia Research Institute; Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Forsey","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia Research Institute; Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn C.","family":"Harper","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia Research Institute; Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia Research Institute; Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7206-675X","authenticated-orcid":false,"given":"Chloe E.","family":"Snider","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia Research Institute; Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9164-1628","authenticated-orcid":false,"given":"Yuanqing","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1339-5959","authenticated-orcid":false,"given":"Sarah A.","family":"Tishkoff","sequence":"additional","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA"},{"name":"Department of Biology, School of Arts and Sciences, University of Pennsylvania; Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9261-244X","authenticated-orcid":false,"given":"Alanna","family":"Strong","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics, Division of Human Genetics, Children\u2019s Hospital of Philadelphia Research Institute; Philadelphia, PA 19104, USA"},{"name":"Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8717-0111","authenticated-orcid":false,"given":"Theodore G.","family":"Drivas","sequence":"additional","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA"},{"name":"Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1614-3909","authenticated-orcid":false,"given":"Colin R.","family":"Goding","sequence":"additional","affiliation":[{"name":"Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford; Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5826-6686","authenticated-orcid":false,"given":"Robert J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Department of Physiology, University of Pennsylvania Perelman School of Medicine; Philadelphia, PA, 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7435-7262","authenticated-orcid":false,"given":"Michael S.","family":"Marks","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia Research Institute; Philadelphia, PA 19104, USA"},{"name":"Department of Pathology and Laboratory Medicine and Department of Physiology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100107101412000_2026.09.27.754807v1.1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-1097.2007.00226.x"},{"key":"2026100107101412000_2026.09.27.754807v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05660"},{"key":"2026100107101412000_2026.09.27.754807v1.3","doi-asserted-by":"publisher","DOI":"10.1006\/jhev.2000.0403"},{"key":"2026100107101412000_2026.09.27.754807v1.4","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1998.00178.x"},{"key":"2026100107101412000_2026.09.27.754807v1.5","doi-asserted-by":"publisher","DOI":"10.1093\/icb\/icab094"},{"key":"2026100107101412000_2026.09.27.754807v1.6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094466"},{"key":"2026100107101412000_2026.09.27.754807v1.7","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0625.12.s2.1.x"},{"key":"2026100107101412000_2026.09.27.754807v1.8","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12167"},{"key":"2026100107101412000_2026.09.27.754807v1.9","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-2-43"},{"key":"2026100107101412000_2026.09.27.754807v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52763-y"},{"key":"2026100107101412000_2026.09.27.754807v1.11","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.2000.130303.x"},{"key":"2026100107101412000_2026.09.27.754807v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01626-1"},{"key":"2026100107101412000_2026.09.27.754807v1.13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009319"},{"key":"2026100107101412000_2026.09.27.754807v1.14","doi-asserted-by":"publisher","DOI":"10.1186\/s12863-019-0765-5"},{"key":"2026100107101412000_2026.09.27.754807v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08147-0"},{"key":"2026100107101412000_2026.09.27.754807v1.16","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105437"},{"key":"2026100107101412000_2026.09.27.754807v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.11.015"},{"key":"2026100107101412000_2026.09.27.754807v1.18","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan8433"},{"key":"2026100107101412000_2026.09.27.754807v1.19","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-015-1559-0"},{"key":"2026100107101412000_2026.09.27.754807v1.20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003372"},{"key":"2026100107101412000_2026.09.27.754807v1.21","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-008-0338-3"},{"key":"2026100107101412000_2026.09.27.754807v1.22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000074"},{"key":"2026100107101412000_2026.09.27.754807v1.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116238"},{"key":"2026100107101412000_2026.09.27.754807v1.24","doi-asserted-by":"publisher","DOI":"10.1126\/science.1213506"},{"key":"2026100107101412000_2026.09.27.754807v1.25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2109934119"},{"key":"2026100107101412000_2026.09.27.754807v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2020.01.012"},{"key":"2026100107101412000_2026.09.27.754807v1.27","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.15732"},{"key":"2026100107101412000_2026.09.27.754807v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2018.05.026"},{"key":"2026100107101412000_2026.09.27.754807v1.29","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1102639"},{"key":"2026100107101412000_2026.09.27.754807v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2022.107560"},{"key":"2026100107101412000_2026.09.27.754807v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.204"},{"key":"2026100107101412000_2026.09.27.754807v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.84"},{"key":"2026100107101412000_2026.09.27.754807v1.33","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103087"},{"key":"2026100107101412000_2026.09.27.754807v1.34","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.009340"},{"key":"2026100107101412000_2026.09.27.754807v1.35","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/94.6.446"},{"key":"2026100107101412000_2026.09.27.754807v1.36","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade6289"},{"key":"2026100107101412000_2026.09.27.754807v1.37","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204011200"},{"key":"2026100107101412000_2026.09.27.754807v1.38","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E06-12-1066"},{"key":"2026100107101412000_2026.09.27.754807v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.06.029"},{"key":"2026100107101412000_2026.09.27.754807v1.40","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124534"},{"key":"2026100107101412000_2026.09.27.754807v1.41","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181a02882"},{"key":"2026100107101412000_2026.09.27.754807v1.42","doi-asserted-by":"publisher","DOI":"10.1101\/gad.324657.119"},{"key":"2026100107101412000_2026.09.27.754807v1.43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0238546"},{"key":"2026100107101412000_2026.09.27.754807v1.44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1810498115"},{"key":"2026100107101412000_2026.09.27.754807v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2025.06.031"},{"key":"2026100107101412000_2026.09.27.754807v1.46","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E11-06-0509"},{"key":"2026100107101412000_2026.09.27.754807v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2021.06.018"},{"key":"2026100107101412000_2026.09.27.754807v1.48","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092667"},{"key":"2026100107101412000_2026.09.27.754807v1.49","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2016.00095"},{"key":"2026100107101412000_2026.09.27.754807v1.50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002861"},{"key":"2026100107101412000_2026.09.27.754807v1.51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0122513"},{"key":"2026100107101412000_2026.09.27.754807v1.52","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0216-1"},{"key":"2026100107101412000_2026.09.27.754807v1.53","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0217"},{"key":"2026100107101412000_2026.09.27.754807v1.54","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201611138"},{"key":"2026100107101412000_2026.09.27.754807v1.55","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218272110"},{"key":"2026100107101412000_2026.09.27.754807v1.56","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2009.00955.x"},{"key":"2026100107101412000_2026.09.27.754807v1.57","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.152.4.809"},{"key":"2026100107101412000_2026.09.27.754807v1.58","unstructured":"S. Vijayasaradhi , Y. Xu , B. Bouchard , A. N. Houghton , \u201cIntracellular Sorting and Targeting of Melanosomal Membrane Proteins: Identification of Signals for Sorting of the Human Brown Locus Protein, GP75.\u201d"},{"key":"2026100107101412000_2026.09.27.754807v1.59","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202005173"},{"key":"2026100107101412000_2026.09.27.754807v1.60","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.351908"},{"key":"2026100107101412000_2026.09.27.754807v1.61","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200907122"},{"key":"2026100107101412000_2026.09.27.754807v1.62","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E06-05-0379"},{"key":"2026100107101412000_2026.09.27.754807v1.63","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.612"},{"key":"2026100107101412000_2026.09.27.754807v1.64","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.11.3451"},{"key":"2026100107101412000_2026.09.27.754807v1.65","doi-asserted-by":"publisher","DOI":"10.1038\/srep44064"},{"key":"2026100107101412000_2026.09.27.754807v1.66","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp415"},{"key":"2026100107101412000_2026.09.27.754807v1.67","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.229500"},{"key":"2026100107101412000_2026.09.27.754807v1.68","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007290"},{"key":"2026100107101412000_2026.09.27.754807v1.69","doi-asserted-by":"publisher","DOI":"10.1038\/jid.1961.42"},{"key":"2026100107101412000_2026.09.27.754807v1.70","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8506"},{"key":"2026100107101412000_2026.09.27.754807v1.71","doi-asserted-by":"publisher","DOI":"10.1002\/biof.29"},{"key":"2026100107101412000_2026.09.27.754807v1.72","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5701063"},{"key":"2026100107101412000_2026.09.27.754807v1.73","doi-asserted-by":"crossref","unstructured":"P. D. Donatien , G. Hunt , C. Pieron , J. Lunec , A. Taieb , A. J. Thody , \u201cThe expression of functional MSH receptors on cultured human melanocytes\u201d (Springer-Verlag, 1992).","DOI":"10.1007\/BF00372074"},{"key":"2026100107101412000_2026.09.27.754807v1.74","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.002"},{"key":"2026100107101412000_2026.09.27.754807v1.75","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-017-0020-9"},{"key":"2026100107101412000_2026.09.27.754807v1.76","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902825116"},{"key":"2026100107101412000_2026.09.27.754807v1.77","doi-asserted-by":"publisher","DOI":"10.1093\/icb\/icab078"},{"key":"2026100107101412000_2026.09.27.754807v1.78","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2005.00240.x"},{"key":"2026100107101412000_2026.09.27.754807v1.79","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.873777"},{"key":"2026100107101412000_2026.09.27.754807v1.80","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.08.019"},{"key":"2026100107101412000_2026.09.27.754807v1.81","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2019.05.003"},{"key":"2026100107101412000_2026.09.27.754807v1.82","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1597696"},{"key":"2026100107101412000_2026.09.27.754807v1.83","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12646"},{"key":"2026100107101412000_2026.09.27.754807v1.84","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E08-05-0456"},{"key":"2026100107101412000_2026.09.27.754807v1.85","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.07.013"},{"key":"2026100107101412000_2026.09.27.754807v1.86","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6530"},{"key":"2026100107101412000_2026.09.27.754807v1.87","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E12-10-0742"},{"key":"2026100107101412000_2026.09.27.754807v1.88","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200302072"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.27.754807","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:22:48Z","timestamp":1790864568000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.27.754807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":88,"URL":"https:\/\/doi.org\/10.64898\/2026.09.27.754807","relation":{},"subject":[],"published":{"date-parts":[[2026,9,28]]},"subtype":"preprint"}}