NRBP2, or Nuclear Receptor Binding Protein 2, is a pseudokinase initially discovered during a screen of neural differentiation genes. It has been shown to play a role in inhibiting tumor progression in various cancers, potentially through its regulation of the 5'-adenosine monophosphate (AMP)-activated protein kinase/ mammalian target of rapamycin (AMPK/mTOR) signaling pathway [1]. NRBP2 is also associated with neural progenitor cell survival and is expressed in specific regions of the developing and adult mouse brain [3].

In breast cancer, NRBP2 is downregulated in tumor tissues compared to normal tissues. Overexpression of NRBP2 in breast cancer cells suppresses cell proliferation, invasion, and the epithelial-mesenchymal transition (EMT), while knockdown reverses these effects. In an orthotopic breast tumor model, NRBP2 overexpression reduces lung metastatic nodules, suggesting its role as a tumor suppressor. The anti-tumor effect may be related to its regulation of the AMPK/mTOR pathway [1].

In hepatocellular carcinoma, NRBP2 expression is downregulated in CD133+ cancer stem cells. Overexpression of NRBP2 restrains cell stemness, increases chemosensitivity, and reduces resistance to chemotherapy agents, likely through the Akt signaling pathway [2].

In medulloblastoma, NRBP2 is downregulated, and its overexpression in cell lines decreases cell numbers, increases cell death, and impairs cell migration and invasion [5].

In thyroid carcinoma, NRBP2 overexpression suppresses tumor growth, reduces the expression of tumor microenvironment markers, macrophage M2 polarization, and angiogenesis [4].

In conclusion, NRBP2 functions as a tumor suppressor in multiple cancers, inhibiting tumor cell growth, invasion, and metastasis, and enhancing chemosensitivity. Its role in neural progenitor cell survival also indicates its importance in normal neural development. The study of NRBP2 knockout or conditional knockout mouse models, though not explicitly detailed in the provided references, would likely further elucidate its functions in these disease conditions and biological processes.