KHNYN is a multidomain endoribonuclease that functions as a key cofactor in antiviral RNA surveillance complexes. The protein contains an N-terminal extended-diKH domain and a C-terminal NYN domain with RNA endonuclease activity 1. KHNYN forms functional complexes with the zinc-finger antiviral protein (ZAP), where it provides the nuclease activity necessary for degrading CpG-rich viral RNAs that ZAP recognizes and binds 21. The NYN domain is a single-stranded RNA ribonuclease that lacks sequence specificity and can digest RNA with or without CpG dinucleotides equivalently in vitro 13. Structurally, the KHNYN KH domain does not bind RNA but contains a negatively charged surface, while the C-terminal domain interacts with ZAP's RNA-binding domain to provide target RNA specificity 1. KHNYN acts redundantly with its homolog N4BP1 in TRIM25-dependent RNA surveillance pathways 4. Importantly, KHNYN can function as an independent restriction factor against CpG-enriched avian viruses, suggesting cell-autonomous antiviral activity beyond its role as a ZAP cofactor 5. The extended-diKH domain is required for antiviral activity and may serve as a protein-protein interaction site for unknown cofactors 6.