EDNRA (endothelin receptor type A) is a G protein-coupled receptor that mediates endothelin-1 (ET-1) signaling with high binding affinity 1. The receptor activates phosphatidylinositol-calcium second messenger systems to regulate diverse physiological processes including vasoconstriction, smooth muscle contraction, and cell proliferation. Mechanistically, EDNRA functions through multiple signaling pathways. ET-1 binding to EDNRA enhances taurine metabolism to promote hair regeneration in dermal papilla cells 1 and modulates HIF-1α through AKT signaling to support glycolytic adaptation in intestinal innate lymphoid cells 2. In fibrotic contexts, pro-fibrotic fibroblasts show elevated EDNRA expression driven by RUNX1-regulated gene networks 3. ENDRA variants associate with multiple diseases. Genetic polymorphisms correlate with ischemic stroke risk—the EDNRA rs5335 CC genotype reduces stroke risk in males while rs1801708 AA increases risk in females 4. EDNRA polymorphisms also associate with migraine susceptibility, particularly the AA genotype of the -231 G>A variant 5. Clinically, EDNRA shows significant oncological relevance. Elevated EDNRA expression predicts poorer outcomes in gastric cancer 6 and correlates with altered tumor immune environments across multiple cancer types 7. EDNRA inhibition suppresses gastric cancer cell proliferation and triggers apoptosis 6, suggesting therapeutic potential in cancer immunotherapy.