ECE-1

Endothelin-converting enzyme-1 (ECE-1) functions as a membrane-bound metalloprotease that catalyzes the conversion of big endothelin to active endothelin-1 (ET-1), regulating vascular tone and endothelial function^[1][2]. Mechanistically, ECE-1 modulates peptide signaling through endosomal pathways, including degradation of internalized neuropeptides such as somatostatin-14, and interacts with receptor trafficking machinery to control cellular responsiveness^[3]. ECE-1 activity is highly relevant in cardiovascular and renal diseases, including systemic hypertension, chronic heart failure, and diabetic nephropathy, as perturbations in ECE-1 expression or activity correlate with pathological ET-1 accumulation^[4][5][2]. Four ECE-1 isoforms (ECE-1a, 1b, 1c, and 1d) arise from alternative promoter usage, sharing catalytic domains but differing in cytosolic tails, which dictate subcellular localization and functional specificity; for example, ECE-1b is retained in late endosomes while ECE-1a localizes to the plasma membrane^[1]. Heterodimerization among isoforms can modulate enzymatic distribution and extracellular activity, suggesting inter-isoform regulation as a potential therapeutic strategy^[1]. Pharmacological studies indicate that selective small-molecule inhibitors, such as SM-19712, can block ECE-1-mediated peptide hydrolysis in acidic endosomes, providing experimental tools for dissecting isoform-specific functions and developing cardiovascular therapeutics^[4][3].