The endothelin A receptor (EDNRA) is a G protein-coupled receptor (GPCR) that binds with high affinity to endothelin-1 (ET-1), a potent vasoconstrictor peptide produced by endothelial cells. EDNRA is primarily expressed on vascular smooth muscle cells, fibroblasts, and certain tumor cells. Upon ET-1 binding, EDNRA activates Gq/11-PLC-IP3 and Rho-ROCK pathways, leading to increased intracellular calcium, smooth muscle contraction, cell proliferation, and extracellular matrix production. In diseases like PAH and systemic sclerosis, overactivation of the ET-1/EDNRA axis drives vascular remodeling, fibrosis, and inflammation.