“…Unlike classical peptide hormones and neuropeptides, which are translated as larger precursor proteins followed by limited proteolytic processing (Holst, 2007, Steiner, 1998), these s(m)ORF-encoded polypeptides (SEPs) are short peptides encoded directly from s(m)ORFs (Galindo et al, 2007, Kondo et al, 2010, Magny et al, 2013, Pauli et al, 2014). A small number of well-studied SEPs have indicated that these polypeptides may act as important regulators in many fundamental biological processes, such as metabolism (Dong et al, 2013), development (Kondo et al, 2010, Pauli et al, 2014), and cell death (Hashimoto et al, 2001), but little is known about the biological activities, regulation, or even total number of SEPs. Therefore, discovery and functional characterization of SEPs will expand our knowledge of the composition of the genome and proteome, and provide fundamental insights into the molecular biology of cells.…”