Ubr7, or Ubiquitin protein ligase E3 component N-recognin 7, is an E3 ubiquitin ligase. It plays crucial roles in multiple biological pathways, including the ubiquitin-proteasome system which is responsible for protein turnover. It has been associated with pathways like glycolysis, immune regulation, and extracellular matrix remodeling, thus being of great biological importance [1,2,3]. Genetic models, such as knockout (KO) mouse models, can be used to study its functions.

In KO or loss-of-function experiments, Ubr7 loss promotes HCC tumorigenesis both in vitro and in vivo by enhancing glycolysis through the Keap1/Nrf2/Bach1/HK2 axis [1]. In TNBC, Ubr7 loss leads to activation of ECM genes and changes in matrix stiffness and invasiveness [3]. In hepatitis B virus-induced HCC, targeting UBR7 catalytic function reduces viral copy numbers, as it ubiquitinates Sp110 to suppress interferon-β mediated immune signaling [4]. In PDAC, depletion of UBR7 increases pancreatic carcinogenesis and gemcitabine resistance by promoting glycolysis [5].

In conclusion, Ubr7 has diverse functions in regulating biological processes. Model-based research, especially KO/CKO mouse models, has revealed its roles in diseases like HCC, TNBC, and PDAC. Understanding Ubr7 is crucial for uncovering disease mechanisms and developing potential therapeutic strategies.