RNASE3 (ribonuclease A family member 3), also known as eosinophil cationic protein (ECP), is a multifunctional antimicrobial and immunomodulatory protein expressed by leukocytes. Primary Function: RNASE3 exhibits broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria through direct cytotoxic mechanisms, including bacterial membrane depolarization and cell content loss 1. Mechanism: The protein operates through both catalytic-dependent and independent modes. Its pro-inflammatory core response activates macrophages via epidermal growth factor receptor (EGFR) pathway activation independent of ribonucleolytic activity, while late-phase antiviral responses depend on catalytic activity 1. RNASE3 protects against Mycobacterium aurum and respiratory syncytial virus infection, with EGFR activation required for antibacterial but not antiviral effects 1. Disease Relevance: RNASE3 polymorphisms are associated with susceptibility to allergic rhinitis, with the G-C-G haplotype conferring increased risk 2. Genetic variants influence severe malaria outcomes; the 371G allele and GGA haplotype increase cerebral malaria susceptibility 34. Clinical Significance: RNASE3 represents a promising biomarker for colorectal cancer early diagnosis, incorporated into diagnostic models achieving AUC >0.90 5. Novel engineered RNase3 peptides show promise against Gram-negative biofilms 6.