HOIP has also been shown to interact with the ISG15 (interferon-induced 15 kDa protein) E3 ligase TRIM25 (tripartite motif-containing 25) [85], an enzyme implicated in the innate immune response against viral infection [86], and Gumby, a linear deubiquitinase involved in modulating the Wnt signalling pathway [87]. This evidence concerns the gene ISG15 and viral infectious disease.