Rreb1, short for Ras-responsive element binding protein 1, is a zinc finger transcription factor. It is widely involved in multiple biological processes such as cell proliferation, transcriptional regulation, and DNA damage repair. The activation of Rreb1 is regulated by the MAPK pathway, and it functions as both a transcriptional repressor and activator. Rreb1 is also a key player in pathways like TGF-β signaling, which is crucial for processes such as epithelial-to-mesenchymal transitions (EMTs) during development, fibrosis, and cancer [1,2].

In a spontaneous mouse model with loss of a nervous system-enriched Rreb1 transcript, there was progressive loss of cerebellar Purkinje cells and ataxia, indicating Rreb1 is essential for neuron survival. Analysis suggested it regulates genes associated with the microtubule cytoskeleton and the endomembrane system, maintaining neuronal proteostasis [3]. In zebrafish lacking rreb1a and rreb1b, and in human pancreatic beta cell models with Rreb1 loss, there were impacts on beta cell mass, insulin expression, and secretion, showing Rreb1's role in glucose homeostasis [4]. In mice, knockdown of Rreb1 in Sertoli cells led to impaired cell development, abnormal blood-testis barrier, and abnormal spermatogenesis, highlighting its importance in spermatogenesis [5].

In conclusion, Rreb1 is vital for various biological functions including neuronal proteostasis, glucose homeostasis, and spermatogenesis. The use of gene knockout models in mice and zebrafish has significantly contributed to understanding Rreb1's role in these processes, providing insights into related diseases such as neurodegenerative disorders, diabetes, and male infertility.