Previous studies showed Hrd1, an ER-localized E3 ligase was responsible for the degradation of nucleoproteins, such as USP15 in response to bacterial infection and METTL14 to suppress ER proteotoxic liver disease, these nucleoproteins would be exported from the nucleus and degraded by the ER-localized E3 ligase Hrd1 (Lu et al, 2019; Wei et al, 2021). Here, USP15 is linked to liver disorder.