{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSCARA5 is a multifunctional receptor belonging to the class A scavenger receptor family that plays key roles in diverse physiological processes. It has been shown to mediate the cellular uptake of negatively charged nanocomplexes—involving oligonucleotides—with contributions from other family members, and to bind the iron‐carrier protein ferritin in a Ca²⁺‐dependent manner, thereby facilitating iron delivery across tissue barriers such as the retina. In addition, a dramatic upregulation of SCARA5 expression during endometrial decidualization in early pregnancy suggests an important role in reproductive physiology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn numerous malignancies—including breast cancer, osteosarcoma, renal cell carcinoma, hepatocellular carcinoma, retinoblastoma, triple‑negative breast cancer, bladder cancer, and nasopharyngeal carcinoma—SCARA5 consistently functions as a tumor suppressor. Its downregulation, often attributable to aberrant promoter hypermethylation or regulation by oncogenic factors such as miR‑141, Rock2, or CSN5, correlates with enhanced cell proliferation, invasion, migration, and reduced apoptosis. Mechanistically, restoration of SCARA5 expression suppresses multiple oncogenic signaling cascades including ERK, AKT, STAT3, FAK, and PI3K/AKT pathways, and modulates processes such as epithelial‑mesenchymal transition. These findings underscore the potential of SCARA5 not only as a critical regulator of cancer progression but also as a promising prognostic marker and therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also implicates SCARA5 in non‐oncogenic contexts. Genetic variants in the SCARA5 gene are associated with plasma levels of coagulation factors such as von Willebrand factor and factor VIII, suggesting a role in circulatory protein clearance. Moreover, altered expression and methylation status of SCARA5 have been explored as diagnostic biomarkers in cancers such as colorectal and oral squamous cell carcinoma, while its modulation in vascular smooth muscle cells affects cellular proliferation and migration—processes that contribute to atherosclerosis and adverse vein graft remodeling. In addition, transcriptome‐based studies in esophageal and other cancers have begun to unravel downstream pathways linked with SCARA5 activity, further emphasizing its multifaceted role in both disease pathogenesis and potential clinical applications."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kariem Ezzat, Henrik Helmfors, Oana Tudoran, et al. 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