{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Leucine‐rich repeat containing protein 15 (LRRC15) is a transmembrane protein that has emerged as an important mediator in diverse pathological contexts, particularly in cancer. In several solid tumors, LRRC15 expression is strongly induced—often by transforming growth factor–β—and is predominantly observed in tumor‐associated fibroblasts as well as in subsets of tumor cells of mesenchymal origin. Its up‐regulation correlates with enhanced cell migration and invasion, contributing to tumor aggressiveness and metastatic potential, as observed in breast cancer, sarcomas, glioblastoma, and ovarian cancer metastases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mechanistically, LRRC15 has been implicated in modulating key signaling pathways. For example, in triple‐negative breast cancer, its overexpression in cancer‐associated fibroblasts promotes invasion by deregulating Wnt/β–catenin signaling and favoring the nuclear accumulation of β–catenin."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In ovarian cancer, LRRC15 facilitates metastasis through its interaction with β1 integrin, thereby activating focal adhesion kinase (FAK) signaling and enhancing adhesion and invasion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, LRRC15 can modulate viral interactions by redistributing receptors required for adenoviral entry, thus dampening adenovirus‐mediated cell death in p53‐based therapies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Owing to its restricted normal tissue expression and prevalent up‐regulation in the tumor microenvironment, LRRC15 has been evaluated as a promising prognostic biomarker and therapeutic target. Preclinical studies have demonstrated promising results using antibody–drug conjugates (ADCs) directed against LRRC15 in osteosarcoma, various sarcomas, and other solid tumors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond oncology, altered LRRC15 expression has been noted in non‐malignant diseases. In osteoarthritis, differential methylation and expression of LRRC15 in chondrocytes suggest a role in coordinating cellular stress responses and extracellular matrix remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Similarly, changes in LRRC15 expression and/or methylation have been observed in maternal blood and placental tissues in the context of intrauterine growth restriction and severe preeclampsia, indicating its potential involvement in developmental and vascular pathologies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Furthermore, differential expression of LRRC15 in periodontal ligament tissues between deciduous and permanent teeth points to its broader role in tissue‐specific remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore that LRRC15 is not only a marker of desmoplastic stroma in tumors but also an active participant in signaling networks that regulate tumor invasion, metastasis, and therapy resistance. Its emerging role as a therapeutic target—particularly via ADC approaches—highlights the translational potential of modulating LRRC15‐mediated pathways in both oncology and other disease states."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "James W Purcell, Sonia G Tanlimco, Jonathan Hickson, et al. 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