Endothelin-converting enzyme 2 (ECE2) belongs to the type II membrane-bound zinc metalloprotease family and shares 59% sequence similarity to ECE1 (Emoto & Yanagisawa1995, Yanagisawa et al. 2000, Lorenzo et al. 2001). In contrast to ECE1, the optimum pH for ECE2 activity is acidic (pH 5.5), which would favor an intracellular localization and a potential role under low pH conditions, for example in ischemia. This difference provides an experimental method for distinguishing between the activities of the two enzymes. ECE2 was found to be localized to the acidified environment of vesicles of the secretory pathway in human endothelial cells but was not detected in Weibel-Palade storage granules (Russell & Davenport 1999).