PGRMC1 (progesterone receptor membrane component 1) is a multifunctional heme-binding protein with diverse cellular roles. Its primary function involves heme homeostasis, acting as a heme chaperone that shuttles newly synthesized heme from mitochondria to cytochrome P450 enzymes and other hemoproteins 1. PGRMC1 binds heme in a five-coordinate high-spin configuration with a tyrosinate ligand at Y95, and demonstrates direct progesterone-binding activity with conformational changes upon ligand binding 2. The protein functions through heme-mediated dimerization, which is necessary for interactions with EGF receptor and cytochrome P450 enzymes, regulating cell proliferation and xenobiotic metabolism 3. In reproductive biology, PGRMC1 has been implicated in primary ovarian insufficiency, with mutations contributing to POI etiology 45. In placental development, PGRMC1 downregulation promotes trophoblast differentiation and fusion, enhancing hCG production 6. Additionally, PGRMC1 functions as a tumor suppressor in hepatocellular carcinoma by blocking c-Myc-induced carcinogenesis through ER stress-independent PERK activation 7. The protein's diverse subcellular localizations and interactions with multiple signaling pathways underscore its central role in cellular homeostasis, reproduction, and cancer prevention.