It is well accepted that the connecting peptide (C-peptide) of proinsulin is a critical element in the biosynthesis of insulin. It facilitates the proinsulin molecule’s proper folding. Following cleavage of proinsulin, the two resultant peptides are stored in secretory granules in the beta-cells and eventually co-released into the circulation in equal concentrations. The possibility that Cpeptide may possess biological activity on its own was a consideration at the time of its discovery in 1968. However, no detectable influence on glucose metabolism in humans, or on lipolysis of isolated fat cells, could be observed. Consequently, the focus on C-peptide as a bioactive peptide diminished, and instead, interest centered on its usefulness as a marker of insulin secretion.