Osr2, or odd-skipped related 2, encodes a zinc-finger containing transcription factor. It is involved in multiple biological processes such as limb, craniofacial, tooth, and kidney development, as well as in processes related to osteoblasts and T-cell function. It is associated with pathways like TCR signaling, Piezo1/calcium/CREB axis, and is regulated by 1,25-dihydroxyvitamin D3 [2,3,8].

In KO mouse models, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8+ T cells or CAR-T cells, suggesting its role as a biomechanical checkpoint aggravating CD8+ T-cell exhaustion in tumors [1]. In tooth development, inactivation of Osr2 rescued molar tooth morphogenesis in Msx1-/-mutant mice and in Runx2-/-mutant mice, with Runx2 expression changes observed in Osr2-/-mutants [4,5]. In palate development, Osr2-/-mutants had impaired palatal shelf growth and cleft palate due to reduced palatal mesenchyme proliferation and altered gene expression patterns [8]. In human endometrial stromal cells, knockdown of OSR2 impairs decidualization, and in gastric cancer patients, OSR2 hypermethylation in serum may have diagnostic value [6,7].

In conclusion, Osr2 is a key regulator in various developmental processes and disease-related cellular functions. Gene knockout mouse models have revealed its importance in tumor immunotherapy (CD8+ T-cell exhaustion), tooth and palate development, and in human endometrial decidualization and gastric cancer diagnosis. Understanding Osr2 provides insights into the underlying mechanisms of these biological processes and diseases, potentially offering new therapeutic strategies.