GCM1 is a transcription factor essential for placental development that acts as a master regulator of trophoblast differentiation 1. It directly activates placenta-specific genes including placental growth factor (PGF) through binding to GCM1-binding sites in gene promoters 2. GCM1 mediates differentiation along both villous and extravillous trophoblast pathways, with its activity antagonized by the stemness factor ΔNp63α; the balance between these factors determines whether trophoblasts remain as stem cells or differentiate 1. GCM1 expression is downregulated under hypoxic conditions (1-2% O₂), characteristic of early placental development, which maintains trophoblast stem cell self-renewal; conversely, GCM1 upregulation is required for syncytiotrophoblast and extravillous trophoblast formation 3. GCM1 regulates critical differentiation genes including CKMT1 and CDKN1C (contact inhibition factor) 13. Clinically, reduced GCM1 expression is associated with preeclampsia and impaired placental development 24. Loss of GCM1 or reduced androgen exposure compromises trophoblast differentiation, contributing to placental dysfunction in conditions like polycystic ovary syndrome 4. These findings establish GCM1 as a central regulatory hub controlling the stemness-differentiation transition in human placental development.