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Related Experiment Video

Updated: Sep 29, 2025

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
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USP30: Structure, Emerging Physiological Role, and Target Inhibition.

Feng Wang1, Yu Gao1, Lihui Zhou1

  • 1Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China.

Frontiers in Pharmacology
|March 21, 2022
PubMed
Summary

Ubiquitin-specific protease 30 (USP30) is a mitochondrial deubiquitinating enzyme crucial for mitophagy and other cellular processes. Inhibiting USP30 shows promise for treating diseases like pulmonary disorders and cancer.

Keywords:
physiological roleregulationstructuretarget inhibitionubiquitin-specific protease 30

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Ubiquitin-specific protease 30 (USP30) is a deubiquitinating enzyme located in the mitochondrial outer membrane and peroxisomes.
  • USP30 possesses a unique catalytic triad and molecular structure, enabling preferential cleavage of Lys6-linked ubiquitin chains.
  • It is regulated by post-translational modifications like phosphorylation and mono-ubiquitination.

Purpose of the Study:

  • To review the current understanding of USP30's structure, regulation, and physiological roles.
  • To summarize the development of USP30 inhibitors for therapeutic applications.
  • To highlight the potential of USP30 as a drug target for various diseases.

Main Methods:

  • Structural studies to elucidate USP30's molecular architecture and catalytic mechanisms.
  • Investigation of USP30's involvement in cellular pathways like mitophagy, pexophagy, apoptosis, and lipogenesis.
  • Analysis of USP30's role in disease pathogenesis.
  • Overview of ongoing research into USP30 inhibitors by academic and industry groups.

Main Results:

  • USP30 plays a critical role in PINK1/Parkin-mediated mitophagy, pexophagy, apoptosis, and lipogenesis.
  • Dysregulation of USP30 is linked to neurodegenerative diseases, cancer, pulmonary disorders, and peroxisome biogenesis disorders.
  • Various classes of USP30 inhibitors are under investigation, with some in pre-clinical development for pulmonary disorders.

Conclusions:

  • USP30 is a significant therapeutic target due to its involvement in fundamental cellular processes and disease.
  • Further research into USP30's structure, function, and inhibition is warranted.
  • USP30 inhibitors hold promise for treating a range of human diseases, including pulmonary disorders and cancer.