RNASEL (ribonuclease L) is an endoribonuclease that functions as a central effector in the interferon-mediated antiviral response 1. Upon viral infection, the OAS-RNASEL pathway is activated: OAS proteins sense double-stranded RNA and generate 2'-5'-oligoadenylates that allosterically activate RNase L 2. Once activated, RNase L cleaves viral and cellular single-stranded RNAs preferentially at UU and UA sequences, inhibiting viral protein synthesis and triggering multiple antiviral mechanisms including apoptosis via JNK-dependent pathways and caspase-1 activation 3. RNase L also globally degrades circular RNAs during innate immune activation, enabling PKR-mediated antiviral responses 4. Beyond antiviral defense, RNase L functions as a regeneration repressor, actively suppressing wound-induced hair neogenesis through caspase-1-mediated cleavage of TRIF, suggesting a trade-off between viral immunity and tissue regeneration 5. Clinically, loss-of-function mutations in RNASEL cause immunodeficiency predisposing to severe COVID-19 complications including multisystem inflammatory syndrome in children 6. Conversely, gain-of-function OAS1 variants activating RNase L cause autoinflammatory disease 3. RNASEL polymorphisms show modest associations with prostate cancer risk in Caucasian populations 78.