Suggested functions for prolyl oligopeptidase: A puzzling paradox

Prolyl oligopeptidase (PO, E.C. 3.4.21.26) is a post-proline cleaving enzyme with endopeptidase activity towards peptides not longer than 30 amino acids. It has been purified and characterized from various mammalian and bacterial sources, but despite its thorough enzymological and structural characterization, the exact function of PO remains obscure. Many investigations have addressed the physiological role of this enzyme, mainly by the use of specific PO inhibitors, activity measurements in clinical samples and (neuro)peptide degradation studies. From the combined results emerges a puzzling paradox: how can an intracellular, cytoplasmatic oligopeptidase affect not only the amount of extracellular neuropeptides but also signal transduction and secretion? This report provides a review of the literature on the suggested functions for PO, highlighting possible pitfalls and contradictions.