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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The 15-leucine-rich repeat containing membrane protein (LRRC15) is a transmembrane protein derived from the leucine-rich repeat (LRR) superfamily that participates in various cell\u2013cell and cell\u2013extracellular matrix interactions, regulating fibrogenesis, vascular invasion, tumorigenesis, and the formation of the innate immune barrier to drive specific antiviral responses. LRRC15, whose expression is reportedly induced by TGF-\u03b2 and IL-1\u03b2 stimulation, was recently found to be associated with the development of skeletal diseases, and its presence has been related to the pathophysiological processes of osteoporosis, osteoarthritis and rheumatoid arthritis. Various transmembrane and intracellular signaling transductions are involved in LRRC15-mediated molecular functions, including integrin, NF-\u03baB, Wnt\/\u03b2-catenin, etc. Additionally, LRRC15 is considered a novel mesenchymal protein and an important biomarker for the occurrence and development of osteosarcoma. Understanding the role of LRRC15 in the bone, joint and tumor microenvironment will facilitate the development of new therapeutic options\u2014particularly LRRC15-based target therapies\u2014for skeletal diseases.<\/jats:p>","DOI":"10.3390\/ijms27156582","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:36:13Z","timestamp":1784878573000},"page":"6582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Molecular Structure, Expression, and Emerging Role of the 15-Leucine-Rich Repeat Containing Membrane Protein (LRRC15) in Skeletal Biology and Diseases"],"prefix":"10.3390","volume":"27","author":[{"given":"Zi-Hao","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Chao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Qing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Zhong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4030-766X","authenticated-orcid":false,"given":"Qian","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0959-440X(01)00266-4","article-title":"The leucine-rich repeat as a protein recognition motif","volume":"11","author":"Kajava","year":"2001","journal-title":"Curr. 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