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Latest high\u2010throughput methods provided huge data sets, revealing an amazing complexity of proteolytic systems important for health and disease. Based on our previous studies, we discuss major problems and questions that have to be solved to gain precise insight into the regulation of the protease web and its impact on pathophysiological conditions. The goal is a combination of different proteomic approaches that help to investigate specific protease function at a glance. Exemplarily, the characterization of the metalloproteases meprin \u03b1 and meprin \u03b2 by proteomic identification of cleavage sites and terminal amine isotopic labeling of substrates demonstrates the power of MS\u2010based techniques. Meprins are rather orphan proteases and could not be assigned to precise biological functions until recently. Proteomics helped to identify meprin \u03b1 and meprin \u03b2 being important for collagen assembly and deposition in skin, which makes them potential therapeutic targets in fibrotic conditions. Additionally, identification of the cleavage site specificity provides the basis for the development of activity\u2010based probes and small compound inhibitors, important for the regulation of meprin activity and subsequent treatment of associated diseases.<\/jats:p>","DOI":"10.1002\/prca.201300079","type":"journal-article","created":{"date-parts":[[2014,1,28]],"date-time":"2014-01-28T11:15:00Z","timestamp":1390907700000},"page":"382-388","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mapping orphan proteases by proteomics: Meprin metalloproteases deciphered as potential therapeutic targets"],"prefix":"10.1002","volume":"8","author":[{"given":"Christoph","family":"Becker\u2010Pauly","sequence":"first","affiliation":[{"name":"Institute of Biochemistry Unit for Degradomics of the Protease Web University of Kiel  Kiel 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