NR2C2 (nuclear receptor subfamily 2 group C member 2) is an orphan nuclear receptor functioning as both a transcriptional repressor and activator. It binds to hormone response elements containing AGGTCA half-site direct repeats and regulates diverse biological processes. NR2C2 represses multiple nuclear receptor signaling pathways including retinoic acid receptor, vitamin D3 receptor, thyroid hormone receptor, and estrogen receptor pathways 1. The receptor plays essential roles in embryonic development, spermatogenesis, and cerebellum development. In testicular inflammation, NR2C2 in macrophages promotes inflammatory cytokine expression (IL-1β, IL-6) via NF-κB pathway activation, subsequently damaging spermatogonia proliferation 2. NR2C2 also represses γ-globin transcription through independent mechanisms from BCL11A 3. Disease relevance includes cancer progression—NR2C2 expression is regulated upstream of DDX41 in liver cancer 4, while miR-4778-3p targets NR2C2 to enhance cervical cancer radiosensitivity 5. Additionally, NR2C2 genetic variants affect cleft lip/palate susceptibility through ARID3B regulation 6, and NR2C2 translation is regulated by arsenic-dependent ALKBH1 demethylation affecting skin tumorigenesis 7. A feedback loop involving lncRNA UCA1-miR-627-5p-NR2C2 regulates glioma malignancy 8. These diverse roles position NR2C2 as a critical transcriptional regulator in development, inflammation, and cancer.