{"doi":"10.1172/jci.insight.149626","title":"Mutations in OSBPL2 cause hearing loss associated with primary cilia defects via sonic hedgehog signaling","abstract":"<jats:p>\n                    Defective primary cilia cause a range of diseases called ciliopathies, which include hearing loss (HL). Variants in the human oxysterol-binding protein like 2 (OSBPL2/ORP2) are responsible for autosomal dominant nonsyndromic HL (DFNA67). However, the pathogenesis of\n                    <jats:italic>OSBPL2</jats:italic>\n                    deficiency has not been fully elucidated. In this study, we show that the\n                    <jats:italic>Osbpl2</jats:italic>\n                    -KO mice exhibited progressive HL and abnormal cochlear development with defective cilia. Further research revealed that OSBPL2 was located at the base of the kinocilia in hair cells (HCs) and primary cilia in supporting cells (SCs) and functioned in the maintenance of ciliogenesis by regulating the homeostasis of PI(4,5)P\n                    <jats:sub>2</jats:sub>\n                    (phosphatidylinositol 4,5-bisphosphate) on the cilia membrane. OSBPL2 deficiency led to a significant increase of PI(4,5)P\n                    <jats:sub>2</jats:sub>\n                    on the cilia membrane, which could be partially rescued by the overexpression of INPP5E. In addition, smoothened and GL13, the key molecules in the Sonic Hedgehog (Shh) signaling pathway, were detected to be downregulated in\n                    <jats:italic>Osbpl2</jats:italic>\n                    -KO HEI-OC1 cells. Our findings revealed that OSBPL2 deficiency resulted in ciliary defects and abnormal Shh signaling transduction in auditory cells, which helped to elucidate the underlying mechanism of OSBPL2 deficiency in HL.\n                  </jats:p>","journal":"JCI Insight","year":2022,"id":599478,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1536358,"name":"Hongshun Wang","orcid":"0000-0003-3089-719X","position":1,"is_corresponding":false},{"id":1499627,"name":"Cheng Zhang","orcid":"0000-0001-7665-8675","position":2,"is_corresponding":false},{"id":1536359,"name":"Yajie Lu","orcid":null,"position":3,"is_corresponding":false},{"id":428503,"name":"Jun Yao","orcid":"0000-0003-2682-8650","position":4,"is_corresponding":false},{"id":399761,"name":"Zhibin Chen","orcid":"0000-0002-1888-6917","position":5,"is_corresponding":false},{"id":1536360,"name":"Guangqian Xing","orcid":null,"position":6,"is_corresponding":false},{"id":1536361,"name":"Qinjun Wei","orcid":null,"position":7,"is_corresponding":false},{"id":1256246,"name":"Xin Cao","orcid":"0000-0001-8787-594X","position":8,"is_corresponding":false},{"id":1536357,"name":"Hairong Shi","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mutations in OSBPL2 cause hearing loss associated with primary cilia defects via sonic hedgehog signaling","abstract":"<jats:p>\n                    Defective primary cilia cause a range of diseases called ciliopathies, which include hearing loss (HL). Variants in the human oxysterol-binding protein like 2 (OSBPL2/ORP2) are responsible for autosomal dominant nonsyndromic HL (DFNA67). However, the pathogenesis of\n                    <jats:italic>OSBPL2</jats:italic>\n                    deficiency has not been fully elucidated. In this study, we show that the\n                    <jats:italic>Osbpl2</jats:italic>\n                    -KO mice exhibited progressive HL and abnormal cochlear development with defective cilia. Further research revealed that OSBPL2 was located at the base of the kinocilia in hair cells (HCs) and primary cilia in supporting cells (SCs) and functioned in the maintenance of ciliogenesis by regulating the homeostasis of PI(4,5)P\n                    <jats:sub>2</jats:sub>\n                    (phosphatidylinositol 4,5-bisphosphate) on the cilia membrane. OSBPL2 deficiency led to a significant increase of PI(4,5)P\n                    <jats:sub>2</jats:sub>\n                    on the cilia membrane, which could be partially rescued by the overexpression of INPP5E. In addition, smoothened and GL13, the key molecules in the Sonic Hedgehog (Shh) signaling pathway, were detected to be downregulated in\n                    <jats:italic>Osbpl2</jats:italic>\n                    -KO HEI-OC1 cells. Our findings revealed that OSBPL2 deficiency resulted in ciliary defects and abnormal Shh signaling transduction in auditory cells, which helped to elucidate the underlying mechanism of OSBPL2 deficiency in HL.\n                  </jats:p>","is_dataset_classified":null,"base_score":2.995732273553991,"endowment":2.995732273553991,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35041619","pmcid":"PMC8876550","openalex_id":"https://openalex.org/W4206322233","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"81771000","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"31571302","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82071052","title":null}],"total_grants":3,"fwci":3.0633,"citation_percentile":0.91623142,"influential_citations":0,"citation_trend":[{"year":2022,"count":2},{"year":2023,"count":5},{"year":2024,"count":4},{"year":2025,"count":6},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"http://insight.jci.org/articles/view/149626/files/pdf","host_type":"journal"},{"url":"http://insight.jci.org/articles/view/149626/files/pdf","host_type":"publisher"},{"url":"https://insight.jci.org/articles/view/149626/files/pdf","host_type":"publisher"},{"url":"https://doi.org/10.1172/jci.insight.149626","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35041619","host_type":"repository"},{"url":"https://doaj.org/article/a76238c501cb4fcbb1d643656cd09ca0","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8876550","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8876550","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC8876550?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Genetic and Kidney Cyst Diseases","Hedgehog Signaling Pathway Studies","Genetic Syndromes and Imprinting","Animals","DNA","DNA Mutational Analysis","Disease Models, Animal","Hair Cells, Auditory","Hearing Loss","Hedgehog Proteins","Mice","Mice, Inbred C57BL","Mice, Transgenic","Mutation","Receptors, Steroid","Signal Transduction","Oxysterol Binding Proteins"],"mesh_terms":["Oxysterol Binding Proteins","Animals","Disease Models, Animal","DNA","DNA Mutational Analysis","Hair Cells, Auditory","Mice, Inbred C57BL","Mice, Transgenic","Mutation","Receptors, Steroid","Signal Transduction","Hearing Loss","Mice","Hedgehog Proteins"],"keywords":["Cilium","Ciliogenesis","Ciliopathy","Smoothened","Hedgehog signaling pathway","Ciliopathies","Cell biology","Biology","Sonic hedgehog","Signal transduction","Hedgehog","Basal body","Genetics","Phenotype","Cytoskeleton","Genetic variation","Otology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"omim"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T08:37:13.290023Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}