biostudies-literatureKumar DSandler FoundationSpanish Ministry of Science, Innovation and UniversitiesUniversity of California, San FranciscoNational Institutes of HealthJane Coffin Childs Memorial Fund for Medical ResearchValencian Council for Innovation, Universities, Science and Digital SocietyChan Zuckerberg Initiativee202011133https://www.ebi.ac.uk/biostudies/studies/S-EPMC8276316biostudies-literatureUnknown220(9)Cells inherit two centrioles, the older of which is uniquely capable of generating a cilium. 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 apThe Journal of cell biologyA ciliopathy complex builds distal appendages to initiate ciliogenesis.PMC8276316R01R01DE029454R01AR054396R01GM124334R01HD089918K99GM126136/R00GM126136PROMETEO/2019/075PCI2018-093062Rains AKrogan NJWestlake CYoder BKShi XKumar DGarcia-Verdugo JMStevenson ESwaney DLReiter JFHuang BHerranz-Perez VLu QfalseA ciliopathy complex builds distal appendages to initiate ciliogenesis.Cells inherit two centrioles, the older of which is uniquely capable of generating a cilium. 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 ap2021-01-01T00:00:00Z2021 Sep2025-04-05T14:05:42.785Z2025-04-05T14:05:42.785ZS-EPMC82763163424163410.1083/jcb.202011133