NRBP2 (Nuclear Receptor Binding Protein 2) is a pseudokinase that functions as a tumor suppressor and regulator of cellular stress responses. The protein is primarily expressed in neural tissues, particularly in cerebellar Purkinje cells and hippocampal neurons, where it promotes neural progenitor cell survival and differentiation 1. NRBP2 mechanistically regulates the AMPK/mTOR signaling pathway, inhibiting cell proliferation, invasion, and epithelial-mesenchymal transition in breast cancer cells 2. The protein also modulates the WNK pathway in response to osmotic stress, functioning as an upstream activator alongside its paralog NRBP1 3. Clinically, NRBP2 expression is frequently downregulated in various cancers including medulloblastoma and breast cancer through epigenetic mechanisms, and its reduced expression correlates with poor patient prognosis 4 2. In cardiac disease, NRBP2 expression changes are associated with left ventricular dysfunction in dilated cardiomyopathy 5. Additionally, NRBP2 can be targeted by miR-25-5p in the PI3K/AKT pathway, affecting cell pyroptosis in bronchopulmonary dysplasia 6. The protein exhibits opposing regulatory functions with NRBP1 in controlling L1 retrotransposition through protein degradation mechanisms 7.