ECE-2

Endothelin-converting enzyme 2 (ECE-2) is a zinc metalloprotease responsible for the proteolytic activation of endothelin precursors, particularly preproendothelin, into biologically active endothelins^[1]. Mechanistically, ECE-2 processes endothelin-1, -2, and -3 via its catalytic activity, integrating with the JNK and ERK1/2 signaling pathways to modulate vascular and airway smooth muscle responses^[1]. In disease models, including murine asthma and vascular dysfunction, ECE-2 activity determines the magnitude of ETB receptor-mediated contractions and endothelial responses, indicating its pivotal role in pathophysiological conditions^[1]. Compared with related isoforms, such as ECE-1, ECE-2 exhibits distinct subcellular localization and preferential regulation under inflammatory conditions, which enables isoform-specific contributions to endothelin signaling^[1]. For experimental applications, selective inhibitors of ECE-2, such as phosphoramidon in combination with pathway-specific modulators, allow dissection of its function in airway hyperreactivity and inflammatory models, preserving the ability to study downstream ET receptor-mediated effects without complete suppression of endothelin generation^[1]. This isoform-specific approach facilitates investigation into therapeutic strategies targeting endothelin-dependent vascular and pulmonary pathologies while minimizing off-target interference from ECE-1 activity^[1].