EDN2 (Endothelin-2) is a 21-amino acid vasoactive peptide encoded on chromosome 1 1 that functions as a potent vasoconstrictor and signaling molecule across multiple physiological systems. As a ligand for endothelin receptors (EDNRA, EDNRB, EDNRB2), EDN2 activates intracellular calcium, MAPK/ERK, and cAMP/PKA signaling pathways 2, regulating smooth muscle contraction, vascular tone, and immune cell function. In reproductive physiology, EDN2 is transiently expressed by granulosa cells during the periovulatory period and critically promotes follicular contraction necessary for ovulation 3. Its expression is regulated by hypoxia via a HIF1A-miR-210-GPD1L axis and cAMP signaling in granulosa-lutein cells 4. Clinically, aberrant EDN2 upregulation contributes to primary open-angle glaucoma (POAG) pathogenesis, correlating with retinal neuroinflammation and ganglion cell injury through NF-κB and Hippo pathway activation 5. Conversely, EDN2 exhibits neuroprotective effects in inherited photoreceptor degeneration, where increased EDN2 expression promotes photoreceptor survival via FGF2-dependent mechanisms 6. Additionally, gram-negative intratumoral bacteria promote cervical cancer lymph node metastasis by upregulating EDN2 through LPS-TLR4/MAPK signaling 7, identifying EDN2 as a potential therapeutic target in cancer progression.