EGLN1 (egl-9 family hypoxia inducible factor 1) encodes PHD2 (prolyl hydroxylase domain protein 2), a critical oxygen sensor that regulates hypoxia-inducible factor (HIF) signaling. Under normoxic conditions, EGLN1/PHD2 catalyzes the hydroxylation of specific proline residues in HIF-1α and HIF-2α, targeting them for proteasomal degradation 1. This hydroxylation requires α-ketoglutarate as a cofactor and can be competitively inhibited by metabolites like 2-hydroxyglutarate and lactate 23. During hypoxia, reduced PHD2 activity allows HIF stabilization, leading to activation of hypoxia-response genes involved in angiogenesis and cellular adaptation 4. Loss-of-function mutations in EGLN1 cause familial erythrocytosis by constitutively activating erythropoietin signaling 1, while specific variants contribute to high-altitude adaptation in Tibetan populations 5. The protein plays roles beyond oxygen sensing, including regulation of hair follicle growth 6 and potential involvement in polycystic ovarian syndrome pathogenesis 7. Therapeutically, EGLN1 represents a promising target for angiogenic therapies and metabolic disorders through modulation of the HIF pathway 4.