Microproteins in Human Physiology and Pathology

Zhenfang Du1,2,3, Felix-Antoine Trifiro4, Marie A Brunet4,5,6

  • 1Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109, United States.

Biochemistry
|March 27, 2026
PubMed

Insights

Researchers are identifying novel microproteins, which are small proteins encoded by small open reading frames (sORFs). This review covers methods for finding these microproteins and their roles in human health and disease, highlighting their therapeutic potential.

Area of Science:

  • Biochemistry
  • Genomics
  • Molecular Biology

Background:

  • Microproteins, defined as polypeptides ≤150 amino acids, are increasingly identified.
  • Small open reading frames (sORFs) encode a growing number of these microproteins.
  • Many microproteins are evolutionarily recent and species-specific.

Purpose of the Study:

  • To review current methodologies for identifying and characterizing novel microproteins.
  • To summarize the biological functions of microproteins in human physiology and pathology.
  • To discuss the translational potential of microproteins in disease diagnosis and therapy.

Main Methods:

  • Integrated application of ribosome profiling (Ribo-Seq), mass spectrometry, and bioinformatics.
  • Comparative genomics and evolutionary analysis for microprotein identification.
  • Functional assays to determine biological activity of identified microproteins.

Main Results:

  • Advances in multi-omics approaches have significantly expanded the catalog of known microproteins.
  • Biologically active microproteins are implicated in essential physiological and pathological processes.
  • Evidence suggests microproteins play crucial roles in human health and disease.

Conclusions:

  • Microprotein research is rapidly evolving, with new identification and characterization techniques emerging.
  • Microproteins represent a promising area for developing novel diagnostic and therapeutic strategies.
  • Further investigation into microprotein functions will unlock their full clinical potential.

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