This systematic review in NR4A2 is focused on three major points: (1) collecting the clinical findings, including three unreported cases, and actualizing the phenotype associated to pathogenic variants in NR4A2; (2) examining its role in neurodegenerative diseases such as Parkinson’s or Alzheimer’s disease; and (3) exploring target-based therapies for these neurological diseases. The gene discussed is NR4A2; the disease is early-onset autosomal dominant Alzheimer disease.