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Using proteomics and superresolved imaging, we identify a module that we term DISCO (distal centriole complex). The DISCO components CEP90, MNR, and OFD1 underlie human ciliopathies. This complex localizes to both distal centrioles and centriolar satellites, proteinaceous granules surrounding centrioles. Cells and mice lacking CEP90 or MNR do not generate cilia, fail to assemble distal appendages, and do not transduce Hedgehog signals. Disrupting the satellite pools does not affect distal appendage assembly, indicating that it is the centriolar populations of MNR and CEP90 that are critical for ciliogenesis. CEP90 recruits the most proximal known distal appendage component, CEP83, to root distal appendage formation, an early step in ciliogenesis. In addition, MNR, but not CEP90, restricts centriolar length by recruiting OFD1. We conclude that DISCO acts at the distal centriole to support ciliogenesis by restraining centriole length and assembling distal appendages, defects in which cause human ciliopathies.<\/jats:p>","DOI":"10.1083\/jcb.202011133","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T02:22:18Z","timestamp":1623723738000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":55,"title":["A ciliopathy complex builds distal appendages to initiate ciliogenesis"],"prefix":"10.1083","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3737-014X","authenticated-orcid":true,"given":"Dhivya","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Addison","family":"Rains","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental, and Integrative Biology, University of Alabama, Birmingham, AL 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1969-1214","authenticated-orcid":true,"given":"Vicente","family":"Herranz-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Biomedical Research Networking Center on Neurodegenerative Diseases, Valencia, Spain 3"},{"name":"Predepartamental Unit of Medicine, Faculty of Health Sciences, Universitat Jaume I, Castell\u00f3 de la Plana, Spain 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanlong","family":"Lu","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Developmental Signaling, Center for Cancer Research, National Cancer Institute Frederick, Frederick, MD 11"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9634-2659","authenticated-orcid":true,"given":"Xiaoyu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 5"},{"name":"Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle L.","family":"Swaney","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 8"},{"name":"California Institute for Quantitative Biosciences, Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 9"},{"name":"J. 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