ZUP1 (zinc finger containing ubiquitin peptidase 1) is a deubiquitinating enzyme (DUB) that defines a previously unrecognized class of evolutionarily conserved cysteine protease DUBs 1. The protein exhibits high selectivity for cleaving long K63-linked polyubiquitin chains through its tandem ubiquitin-binding domains, while showing poor activity against mono- or di-ubiquitin substrates and weak activity against K11- and K48-linked chains 231. ZUP1 has a modular architecture with four N-terminal zinc finger domains and a C-terminal deubiquitinase domain that shares structural similarity with UFM1- and Atg8-specific proteases 24. The enzyme plays crucial roles in genome stability by being recruited to genotoxic stress sites and regulating K63-ubiquitin conjugates during replication stress, promoting chromosome 6 in a catalytically-dependent manner 1. Additionally, ZUP1 modulates ubiquitination of replication protein A (RPA) complex proteins in response to replication stress 3. Recent studies have revealed ZUP1's function in innate immunity as a key component of the MAVS complex, where it enhances antiviral signaling by binding viral RNA through its zinc finger domains and facilitating type I interferon production 45. ZUP1 expression is upregulated during viral infection, and its deficiency increases susceptibility to viral infections 4.