Among the genes upregulated during infection is IFN-stimulated gene 15 (ISG15) (MacQuillan et al., 2003; Robinson et al., 2015), a small ubiquitin-like protein that covalently attaches to lysine residues on target substrates through post-translational modification (Loeb & Haas, 1992; Potter et al., 1999). The gene discussed is ISG15; the disease is infection.