Interferon-stimulated 20 kDa protein (ISG20) is an exoribonuclease that functions as part of the host innate immune response to RNA-based viruses. Indeed, expression of ISG20 can be induced by type-I and type-II interferons following cellular exposure to RNA-based viruses. Mechanistically, ISG20 localizes to the nucleolus and is believed to inhibit the replication of RNA-based viruses, in part, by employing 3'-5' exonuclease activity toward viral RNAs.