NANOG is a core transcription factor essential for maintaining pluripotency and self-renewal in embryonic stem cells. It functions as part of a regulatory network with OCT4 and SOX2, where these factors co-occupy target genes and form autoregulatory and feedforward loops to sustain stem cell identity 1. NANOG binds to its own promoter and can autoregulate its expression during differentiation 1. The protein operates through phase separation mechanisms, particularly with TAZ, to enhance transcription of pluripotency genes like SOX2 and OCT4 2. During normal development, NANOG expression is crucial for preimplantation development and progressively decreases as embryonic stem cells differentiate, becoming undetectable in most adult tissues 3. However, NANOG re-expression occurs in cancer, where it enables cancer cells to acquire stem-cell-like properties associated with tumor growth, metastasis, and treatment resistance 3. In adult endothelium, low-level NANOG expression maintains endothelial cell homeostasis by regulating telomerase and eNOS expression 4. Clinically, high NANOG expression in cancers correlates with poor prognosis, advanced stage, and treatment resistance, making it a promising prognostic biomarker 5. Two newly discovered enhancers regulate NANOG expression and are critical for balancing self-renewal and differentiation in human embryonic stem cells 6.