Polypeptides which are related to the neprilysin enzyme family and have zinc metalloprotease activities and are referred to as IGS5, polynucleotides encoding such polypeptides, vectors containing such polynucleotides, host cells containing such vectors, processes for producing such polypeptides and/or polynucleotides, screening methods for identifying compounds which stimulate or inhibit IGS5 polypeptides and/or polynucleotides, and the use of such polypeptides and/or polynucleotides in therapy of various dysfunctions, disorders or diseases, particularly cardiovascular diseases, metabolic diseases such as diabetes mellitus type II, and neurodegenerative disorders, such as Parkinson's Disease.