{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRCN1 is an endoplasmic reticulum–resident calcium‐binding protein characterized by six EF‐hand motifs that bind Ca²⁺ in a cooperative manner, resulting in conformational changes that increase its α‐helical content and modulate the secretory pathway and intracellular homeostasis. Proteomic analyses have documented its overexpression in renal cell carcinoma tissues, and its molecular behavior is distinct from related CREC family members (for example, unlike calumenin it does not bind thrombospondin‐1). In murine models, deletion of a genomic region including RCN1 has been linked to severe ocular defects, underscoring its potential developmental roles."}, {"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": "\nElevated expression of RCN1 has been observed in a wide range of malignancies—including prostate, non–small cell lung, nasopharyngeal, uterine sarcoma, acute myeloid leukemia, and esophageal squamous cell carcinomas—where it promotes tumor cell viability, proliferation, migration, and invasion. Functional studies indicate that downregulation of RCN1 provokes endoplasmic reticulum stress (via PERK‐eIF2α activation) and triggers caspase‐dependent apoptosis, necroptosis, or pyroptosis by affecting key signaling mediators such as AKT, CaMKII, and interferon pathways. Moreover, RCN1 upregulation has been associated with resistance to chemotherapeutic agents and even hypoxia‐induced radioresistance, highlighting its potential as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its intracellular functions, RCN1 is emerging as a promising biomarker with diagnostic and prognostic relevance. Its aberrant expression has been detected in the secretomes of fibrotic fibroblasts from diseases such as systemic sclerosis and in tumor‐associated lymphatic endothelial cells, and its cell surface localization on endothelial and cancer cells may modulate adhesion and contribute to metastatic dissemination. Further, RCN1 appears to influence the polarization of tumor‐associated macrophages, integrating its role into the complex tumor microenvironment seen in oral cancer and other malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "13", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Giuliana Giribaldi, Giovanna Barbero, Giorgia Mandili, et al. 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