EDN1 encodes endothelin-1, a potent vasoconstrictor peptide that serves as a critical regulator of vascular function and development. The primary function of EDN1 involves binding to G-protein coupled receptors EDNRA and EDNRB, activating downstream signaling cascades including PTK2B, BCAR1, BCAR3, and GTPases RAP1 and RHOA in glomerular mesangial cells 1. Mechanistically, EDN1 promotes arterial wall remodeling through ROCK signaling activation and subsequent nuclear translocation of NFATC3, which induces transcription of smooth muscle hypertrophy markers like ACTA2 1. During development, endothelin signaling plays crucial roles in neural crest cell maturation and tissue formation 2. Disease relevance includes significant associations with pulmonary arterial hypertension, where EDN1 rs5370 polymorphisms increase PAH risk substantially 3. Additionally, GCN2 kinase mediates hypoxia-induced EDN1 expression via HIF-2α, contributing to pulmonary vascular remodeling and PAH pathogenesis 4. Clinically, EDN1 represents a β-catenin target gene involved in organ fibrosis and cancer-related processes 5, and the nearby PHACTR1 locus influences EDN1 transcription in fibromuscular dysplasia 6. EDN1 transcriptional regulation is tightly controlled through multiple tissue-specific mechanisms 7.