ZNRF2 (zinc and ring finger 2) is an E3 ubiquitin ligase that plays critical roles in neuronal function and has emerging significance in cancer biology. In the nervous system, ZNRF2 localizes to presynaptic plasma membranes and contributes to the establishment and maintenance of neuronal transmission and plasticity 1. The protein regulates key cellular processes through its ubiquitin ligase activity, including targeting proteins for degradation and modulating autophagy pathways 2. ZNRF2 acts as a positive regulator of mTORC1 activation by amino acids, with mTOR phosphorylation creating a self-regulating feedback mechanism 2. In cancer contexts, ZNRF2 demonstrates oncogenic properties across multiple tumor types, with elevated expression correlating with poor prognosis in gliomas, osteosarcoma, and lung adenocarcinoma 345. The protein promotes cancer cell proliferation through various mechanisms, including enhancement of glycolysis in glioblastoma and regulation of ferroptosis resistance in lung adenocarcinoma via SLC3A2 membrane translocation 35. Additionally, ZNRF2 shows protective effects in cerebral ischemia-reperfusion injury by inhibiting excessive autophagy 2. These diverse functions establish ZNRF2 as both a critical regulator of normal neuronal physiology and a potential therapeutic target in cancer treatment.