{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FKBP10 encodes an endoplasmic reticulum–resident peptidyl‐prolyl cis–trans isomerase known as FKBP65, which plays a critical role in the posttranslational maturation of fibrillar collagens, particularly type I procollagen. Multiple genetic studies have demonstrated that loss‐of‐function mutations in FKBP10 disrupt normal collagen folding and trimer stabilization, leading to deficient secretion and abnormal extracellular cross‐link formation. This defect in collagen processing underlies a spectrum of connective tissue disorders—including recessive osteogenesis imperfecta and Bruck syndrome—characterized by bone fragility, joint contractures, and reduced hydroxylation of collagen telopeptide lysine residues necessary for proper cross‐linking."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functional analyses in patient‐derived fibroblasts and mouse models further reveal that deficiency of FKBP65 leads to intracellular retention of procollagen, expansion of the endoplasmic reticulum, and defective deposition of mature collagen fibrils in the extracellular matrix, thereby compromising the structural integrity of bone and other connective tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its well‐established role in collagen homeostasis, aberrant FKBP10 expression has been correlated with cancer progression. In gastric and lung cancer, elevated levels of FKBP10 have been linked to enhanced cell growth, increased tumor stemness, and poorer patient outcomes, likely via its peptidyl–prolyl isomerase activity that may influence protein folding and cellular signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, FKBP10 (FKBP65) is a pivotal molecular chaperone essential for proper type I procollagen folding, secretion, and extracellular matrix assembly. Its dysfunction not only disrupts bone matrix integrity leading to osteogenesis imperfecta and Bruck syndrome but may also contribute to tumor progression through its roles in protein processing.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yasemin Alanay, Hrispima Avaygan, Natalia Camacho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2010.02.022"}], "href": "https://doi.org/10.1016/j.ajhg.2010.02.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20362275"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20362275"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Brian P Kelley, Fransiska Malfait, Luisa Bonafe, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/dds371"}], "href": "https://doi.org/10.1093/hmg/dds371"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22949511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22949511"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Maria Trinidad Puig-Hervás, Samia Temtamy, Mona Aglan, et al. 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