NR4A3 (nuclear receptor subfamily 4 group A member 3) is a transcriptional regulator that functions as both an activator and repressor depending on cellular context. As a transcriptional activator, NR4A3 binds to nuclear receptor binding elements (NBRE) and Nur response elements (NurRE) to regulate target gene expression 1. The protein plays crucial roles in vascular biology, promoting smooth muscle cell proliferation and vascular calcification through direct transcriptional activation of glycolytic genes ALDOA and PFKL, leading to enhanced lactate production and histone lactylation 1. In cardiac tissue, NR4A3 maintains mitochondrial energy metabolism and reduces oxidative stress by preserving SDHA transcription, protecting against diabetes-induced atrial cardiomyopathy 2. However, NR4A3 also functions as a negative regulator in immune responses, limiting CAR T cell function in solid tumors by promoting T cell exhaustion and hyporesponsiveness 34. In cardiac reprogramming, NR4A3 acts as a senescence-promoting factor that blocks fibroblast-to-cardiomyocyte conversion by maintaining fibrotic and inflammatory gene programs 5. Clinically, NR4A3 serves as a diagnostic marker in salivary gland neoplasms and is associated with poor prognosis in Helicobacter pylori-related gastric cancer 67. The protein's context-dependent regulatory functions make it both a potential therapeutic target and biomarker across diverse pathological conditions.