Microproteins in Human Physiology and Pathology

Microproteins are defined as polypeptides of 100-150 or fewer amino acids. With the integrated application of ribosome profiling (Ribo-Seq), mass spectrometry, and bioinformatic approaches, more microproteins have been identified as being encoded by small open reading frames (sORFs). The majority of microproteins are evolutionarily young and may represent species-specific events. This review highlights the current methods and their challenges for identification and characterization of novel microproteins. We will also summarize the biologically active microproteins that are involved in biological processes and essential for human physiology and pathology, followed by a discussion of their significant translational potential for diagnosis, prognosis, and therapeutic intervention in human diseases.