Znrf2, an E3 ubiquitin ligase, is involved in multiple biological processes. It plays a role in regulating the Na⁺/K⁺ATPase along with ZNRF1 [4]. Znrf2 also participates in the mTORC1 pathway, as it is a substrate of mTORC1 and regulates its activation by amino acids [6].

Znrf2 has been implicated in numerous disease conditions. In cancer, it generally shows higher expression in tumors compared to normal tissues. For example, in non-small cell lung cancer (NSCLC), high Znrf2 levels are correlated with poor prognosis, and its overexpression promotes cell growth and suppresses apoptosis, while depletion has the opposite effects [5]. In breast cancer, Znrf2 is highly expressed, and its silencing suppresses cell proliferation and induces apoptosis [2]. In glioma, Znrf2 expression is elevated, and its knockdown impairs cell proliferation, cell cycle progression, and glycolysis [3]. Additionally, in cerebral ischemia/reperfusion injury, overexpression of Znrf2 has a protective effect by inhibiting mTORC1-mediated autophagy [1].

In conclusion, Znrf2 is a key E3 ubiquitin ligase involved in important cellular regulatory pathways. Its dysregulation is associated with various diseases, especially cancer. Studies, including those using functional assays like knockdown experiments in different cell lines, have revealed its oncogenic roles in multiple cancers, highlighting its potential as a therapeutic target in these disease areas.