Ubr5, also known as ubiquitin protein ligase E3 component n-recognin 5, is an E3 ubiquitin ligase belonging to the HECT E3 ligase family. It plays a crucial role in regulating various physiological functions such as cell proliferation, autophagy, apoptosis, and cell cycle progression by catalyzing ubiquitin chains on target proteins [4]. Ubr5 is involved in multiple biological pathways, including those related to the immune response, virus infection, DNA damage response, and protein quality control [4].

Ubr5 deficiency in cell line models has shown significant impacts. In triple-negative breast cancer (TNBC), Ubr5 deficiency affects IFN-γ-induced PDL1 transcription, and restoring PD-L1 expression in UBR5-deficient tumor cells recoups their malignancy in vivo [1]. In ovarian cancer, tumor-derived UBR5 promotes cancer growth and metastasis by inducing immunosuppressive macrophages, and OC-specific targeting of UBR5 enhances the survival benefit of chemotherapy and immunotherapies [2]. In colorectal cancer, UBR5 mediates chemoresistance by inhibiting ferroptosis, and targeting UBR5 with a ferroptosis inducer sensitizes CRC to oxaliplatin-induced cell death [3]. In antiviral immunity, Ubr5 knockout mice are more susceptible to lethal RNA virus infection as UBR5 deficiency reduces antiviral immune responses to RNA viruses [5].

In conclusion, Ubr5 is essential in multiple biological processes. Through gene knockout models in various disease areas like breast, ovarian, and colorectal cancers, as well as in antiviral immunity, Ubr5 has been shown to play key roles in tumor progression, immune evasion, chemoresistance, and antiviral responses. Understanding Ubr5's functions through these models provides potential therapeutic targets for treating related diseases.