{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRNASE2, also known as eosinophil‐derived neurotoxin (EDN), is a multifunctional ribonuclease that plays a pivotal role in innate immunity. It not only exhibits potent ribonucleolytic activity responsible for the direct destruction of viral RNA (for example, in respiratory syncytial virus) but also acts as an endogenous “alarmin” by activating dendritic cells via Toll‐like receptor pathways (including TLR2 and TLR8 after processing in concert with RNase T2). These actions help promote antigen‐specific Th2 immune responses and contribute to antiviral host defense."}, {"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": "\nAt the molecular and structural level, detailed crystallographic analyses have revealed that RNASE2 possesses unique features—such as a distinct N‐terminal segment that modulates its cytotoxicity and binding affinities to inhibitors—and that it can be displayed on the surface of granulocytes via glycosylphosphatidylinositol anchors. In addition, expression studies have uncovered intricate regulatory mechanisms including the contribution of noncoding RNAs and promoter elements that govern EDN synthesis in maturing eosinophils, while mutations or polymorphisms in its gene further underscore its finely tuned regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, altered RNASE2/EDN expression and genetic variation have been closely associated with a range of inflammatory and allergic disorders—including asthma, atopic dermatitis, eosinophilic esophagitis, and even systemic lupus erythematosus—thereby establishing its value as a biomarker. Measurements of EDN levels in serum, urine, and tissue specimens correlate with disease severity and airway hyperresponsiveness, and studies of its genetic polymorphisms support its potential role in predisposing individuals to multifactorial immune‐mediated conditions. These observations highlight the translational relevance of RNASE2 both in disease monitoring and as a candidate for future therapeutic targeting."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J B Domachowske, C A Bonville, K D Dyer, et al. 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