NFIX is a sequence-specific DNA-binding transcription factor that recognizes palindromic sequences in promoters and regulatory regions 1. It functions as both a transcriptional activator and repressor, with roles spanning multiple developmental and physiological processes. In retinal development, NFIX regulates mitotic exit and late-born cell specification, controlling bipolar interneuron and Müller glia fate while promoting progenitor quiescence 2. NFIX cooperates with NFIA to silence fetal hemoglobin genes in adult erythroid cells by directly repressing HBG1/2 and stimulating BCL11A expression, relevant to sickle cell disease and β-thalassemia treatment 1. A circular RNA form of NFIX (circNfix) suppresses cardiomyocyte proliferation and is downregulated to promote cardiac regeneration after myocardial infarction 3. NFIX plays context-dependent roles in cancer: it regulates oxidative stress responses and cell fate, with both tumor-promoting and tumor-suppressing functions depending on cancer type 4. In kidney fibrosis, NFIX promotes apoptosis by upregulating Ifi27, contributing to disease progression 5. Pathogenic NFIX mutations cause developmental disorders: Malan syndrome features intellectual disability, growth abnormalities, and anxiety, while Marshall-Smith syndrome presents with developmental delay and skeletal abnormalities 6 7. NFIX also coordinates with EZH2 to regulate medulloblastoma metastasis through neurodevelopmental pathways 8.