The Small Open Reading Frame‐Encoded Peptides: Advances in Methodologies and Functional Studies

Abstract Small open reading frames (sORFs) are an important class of genes with less than 100 codons. They were historically annotated as noncoding or even junk sequences. In recent years, accumulating evidence suggests that sORFs could encode a considerable number of polypeptides, many of which play important roles in both physiology and disease pathology. However, it has been technically challenging to directly detect sORF‐encoded peptides (SEPs). Here, we discuss the latest advances in methodologies for identifying SEPs with mass spectrometry, as well as the progress on functional studies of SEPs.