This study identifies a novel human zinc metalloprotease, angiotensin-converting enzyme homolog (ACEH), which shares significant homology with human angiotensin-converting enzyme (ACE) (40% identity and 61% similarity). ACEH contains a single HEXH zinc-binding domain and is predicted to be a 92.4 kDa glycosylated protein. Expression of a soluble, truncated form of ACEH in Chinese hamster ovary (CHO) cells produces a 120 kDa glycoprotein that cleaves angiotensin I and angiotensin II but not bradykinin or Hip-His-Leu. ACEH functions exclusively as a carboxypeptidase, inhibited by EDTA but not by classical ACE inhibitors like captopril, lisinopril, or enalaprilat. The genomic sequence of ACEH reveals 18 exons, with several exons sharing size similarities with human ACE. Northern blot analysis shows high expression of ACEH mRNA in testis, kidney, and heart. These findings suggest that ACEH may play a role in cardiovascular and renal function, as well as fertility.This study identifies a novel human zinc metalloprotease, angiotensin-converting enzyme homolog (ACEH), which shares significant homology with human angiotensin-converting enzyme (ACE) (40% identity and 61% similarity). ACEH contains a single HEXH zinc-binding domain and is predicted to be a 92.4 kDa glycosylated protein. Expression of a soluble, truncated form of ACEH in Chinese hamster ovary (CHO) cells produces a 120 kDa glycoprotein that cleaves angiotensin I and angiotensin II but not bradykinin or Hip-His-Leu. ACEH functions exclusively as a carboxypeptidase, inhibited by EDTA but not by classical ACE inhibitors like captopril, lisinopril, or enalaprilat. The genomic sequence of ACEH reveals 18 exons, with several exons sharing size similarities with human ACE. Northern blot analysis shows high expression of ACEH mRNA in testis, kidney, and heart. These findings suggest that ACEH may play a role in cardiovascular and renal function, as well as fertility.