NR4A2 is a transcription factor in the nuclear receptor superfamily with dual roles in neuronal development and immune regulation. Primary function: NR4A2 is crucial for differentiation and maintenance of mesencephalic dopaminergic neurons, regulating expression of genes including SLC6A3, SLC18A2, TH, and DRD2 essential for dopaminergic neuron development 1. Mechanism: NR4A2 functions as a DNA-binding transcription factor that regulates gene expression through multiple epigenetic mechanisms including DNA methylation, histone deacetylation, and microRNA regulation 2. Beyond neuronal development, NR4A2 is activated in immune cells under chr2 stimulation, promoting T cell exhaustion through alterations in chr2 accessibility and transcriptional programs 3. In microglia, NR4A2 activation dysregulates cholesterol homeostasis via SQLE, contributing to protumorigenic immune responses 4. Disease relevance: Pathogenic NR4A2 variants cause developmental delay, intellectual disability, language impairment, and early-onset dystonia-parkinsonism 5. Reduced NR4A2 expression associates with neurodegeneration including Parkinson's and Alzheimer's disease 2. NR4A2 overexpression worsens sepsis outcomes in CD4+ T cells 6. Clinical significance: NR4A2 inhibition enhances CAR-T cell efficacy against solid tumors by preventing exhaustion 7, and NR4A2-targeted therapies show promise for neurodegenerative diseases and cancer immunotherapy.