ISG15 has been shown to be involved in some subtypes of breast cancer, including TNBC (Hadjivasiliou, 2012; Burks et al., 2014; Forys et al., 2014), and UBE2L6/UBCH8, a ubiquitin conjugating E2 enzyme, has been reported to mediate ISG15 conjugation (Zhao et al., 2004). Here, UBE2E2 is linked to breast cancer.