{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSecreted phosphoprotein 24 kD, encoded by SPP2, is a multifunctional extracellular matrix protein that plays a central role in bone metabolism. Studies have demonstrated that full‐length SPP24 (the protein product of SPP2) binds with high affinity to bone morphogenetic proteins (BMPs), thereby modulating their bioavailability. Interestingly, the protein undergoes proteolytic cleavage to generate truncated products with distinct activities, wherein the full‐length form can inhibit ectopic bone formation while smaller fragments (such as spp18.5) may promote osteogenesis. SPP2 is predominantly transcribed in the liver and bone, and its gene structure and regulation by hormones and transcription factors further underscore its importance in skeletal development and turnover."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in bone biology, SPP2 appears to have significant implications in cancer and retinal disorders. Systematic assessments suggest that SPP2 might serve as a prognostic marker in various cancers, with studies reporting its potential to attenuate BMP2‐induced tumor growth in models of prostate cancer and osteosarcoma through interference with Smad signaling pathways. In contrast, mutations in SPP2 that affect critical structural domains lead to protein mislocalization and toxic accumulation in photoreceptors, thereby contributing to the pathogenesis of retinitis pigmentosa. These contrasting roles highlight the context‐dependent functions of SPP2 in cell proliferation and differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther extending its clinical relevance, circulating levels of SPP24 have been correlated with renal function and other markers of mineral metabolism, suggesting a regulatory role in systemic calcification processes. In addition, recent genomic studies investigating hepatocellular carcinoma prognosis have identified SPP2 as one of the key genes potentially impacting patient outcomes, thereby reinforcing its emerging importance as both a biomarker and a possible therapeutic target in diseases beyond the skeletal system."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Elsa J Brochmann, Keyvan Behnam, Samuel S Murray "}, {"type": "b", "children": [{"type": "t", "text": "Bone morphogenetic protein-2 activity is regulated by secreted phosphoprotein-24 kd, an extracellular pseudoreceptor, the gene for which maps to a region of the human genome important for bone quality."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Metabolism (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.metabol.2009.01.001"}], "href": "https://doi.org/10.1016/j.metabol.2009.01.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19375587"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19375587"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Clare S Bennett, Hamid R Khorram Khorshid, J Alexandra Kitchen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the human secreted phosphoprotein 24 gene (SPP2) and comparison of the protein sequence in nine species."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Matrix Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.matbio.2003.12.001"}], "href": "https://doi.org/10.1016/j.matbio.2003.12.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15062857"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15062857"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Samuel S Murray, Jeffrey C Wang, Maria Eugenia Leite Duarte, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The bone matrix protein secreted phosphoprotein 24 kD (Spp24): bone metabolism regulator and starting material for biotherapeutic materials."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histol Histopathol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14670/HH-30.531"}], "href": "https://doi.org/10.14670/HH-30.531"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25339413"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25339413"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Haijun Tian, Chen-Shuang Li, Ke-Wei Zhao, et al. 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