OSR2 is a zinc finger-containing transcription factor with diverse roles in developmental and pathological processes. During embryogenesis, OSR2 regulates skeletal development, limb morphogenesis, and craniofacial patterning, including mandibular molar tooth development and palatogenesis through interactions with PAX9 and other developmental regulators 1. OSR2 promotes chondrocyte differentiation and maintains articular cartilage homeostasis through H3K36 methylation-dependent mechanisms; decreased OSR2 expression associates with osteoarthritis pathogenesis, and OSR2 restoration improves cartilage homeostasis in disease models 2. OSR2 expression is upregulated by 1,25-dihydroxyvitamin D3 in osteoblasts and is involved in osteogenic differentiation of dental follicle cells 34. In the nervous system, OSR2 specifically marks and regulates mural lymphatic endothelial cell differentiation and maintenance, controlling their transition to scavenger cells through cadherin-6 regulation 5. Beyond development, OSR2 functions as a biomechanical checkpoint integrating TCR signaling and mechanical stress through the Piezo1/calcium/CREB axis to promote exhaustion of tumor-reactive CD8+ T cells, and its depletion enhances anti-tumor immunity 6. Clinically, OSR2 methylation serves as a biomarker for gastric cancer detection 7, and MAX-regulated OSR2 expression is critical for endometrial decidualization, with reduced OSR2 associated with recurrent spontaneous abortion 8.