Interferon-induced ISG15-specific protease that plays a crucial role for maintaining a proper balance of ISG15-conjugated proteins in cells. Regulates protein ISGylation by efficiently cleaving ISG15 conjugates linked via isopeptide bonds. Regulates T-cell activation and T-helper 17 (Th17) cell differentiation by deubiquitinating TAK1, likely to keep TAK1-TAB complexes in steady conditions. In turn, restricts activation of NF-kappa-B, NFAT, and JNK as well as expression of IL2 in T-cells after TCR activation. Acts as a molecular adapter with USP20 to promote innate antiviral response through deubiquitinating STING1. Involved also in the negative regulation of the inflammatory response triggered by type I interferon. Upon recruitment by STAT2 to the type I interferon receptor subunit IFNAR2 interferes with the assembly of the ternary interferon-IFNAR1-IFNAR2 complex and acts as a negative regulator of the type I interferon signaling pathway.; [Isoform 2]: Has enzymatic activity similar to isoform 1 and interferes with type I interferon signaling. Major deISGylation enzyme for nuclear proteins.