It has been reported that the endoplasmic reticulum-located E3 ubiquitin ligase Hrd1 can also ubiquitinate and interact with USP15 at the K21 residue in HEK293T cells, which does not cause USP15 to be degraded, but it loses its activity for IκBα deubiquitination during bacterial infection, leading to the excessive activation of NF-κB. The gene discussed is USP15; the disease is bacterial infectious disease.