{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPGRMC1 plays a central role in metabolic regulation by interacting with key cytochrome P450 enzymes that catalyze steroid and cholesterol biosynthesis. Structural and biochemical studies have revealed that PGRMC1 binds heme in a unique high‐spin, five‐coordinate configuration, suggesting that it may act as a heme chaperone or sensor to regulate heme release from ferrochelatase and stabilize P450 enzymes. In addition, PGRMC1 exerts isoform‐specific modulation of drug‐metabolizing P450 activities and thereby influences hepatic detoxification and metabolic homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn oncogenesis, PGRMC1 contributes to tumor progression by enhancing cell proliferation, increasing chemoresistance, and facilitating metastatic behavior. It achieves these effects in part by stabilizing receptors such as EGFR and engaging with cytochrome P450 enzymes to influence the metabolism of chemotherapeutic agents. Overexpression of PGRMC1 is associated with anti‐apoptotic signaling, augmented cellular migration, and aberrant growth factor signaling, which collectively make it a promising biomarker and therapeutic target in a variety of cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn reproductive and developmental contexts, PGRMC1 acts as an adaptor protein that facilitates the trafficking and membrane localization of non‐classical progesterone receptors, thereby mediating rapid, non‐genomic progestin actions. Its expression in ovarian, endometrial, placental, and sperm cells underlies its involvement in processes such as cell survival, differentiation, and steroid signaling. Alterations in PGRMC1 expression or mutations that impair its interaction with key partners have been linked to reproductive dysfunctions including premature ovarian failure, aberrant trophoblast differentiation, and endometriosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "35"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond metabolism and reproduction, PGRMC1 modulates cellular stress responses, autophagy, and metabolic reprogramming. It influences insulin receptor trafficking and thereby regulates glucose uptake, while post‐translational modifications of PGRMC1 contribute to shifts toward aerobic glycolysis (the Warburg effect) and impact stem cell self‐renewal. 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