Antibodies against eosinophil-derived neurotoxin (EDN), a major granule protein of eosinophils, have been identified in a subset of patients with eosinophilic and autoimmune disorders. EDN is a secreted ribonuclease released during eosinophil activation and degranulation and has been implicated in inflammatory signaling, immune responses, and host defense. Autoantibodies directed against EDN may reflect eosinophil activation, tissue injury, and alterations in immune tolerance. The presence of anti-EDN antibodies has been investigated in association with eosinophil-related immune dysregulation and may provide a tool for studying autoreactive immune responses involving eosinophil granule proteins. EDN, also known as RNase 2, belongs to the pancreatic-type ribonuclease superfamily and is predominantly expressed and stored in eosinophil secondary granules. The detection of anti-EDN antibodies is being investigated for its potential role in understanding autoimmune mechanisms, eosinophil-associated inflammation, and biomarker development in eosinophilic and inflammatory disorders.