USP30, also known as Ubiquitin Specific Peptidase 30, is an enzyme belonging to the deubiquitinating enzyme (DUB) family. DUBs are responsible for the removal of ubiquitin, a small protein that acts as a tag to mark other proteins for degradation or to regulate their functions within cells. USP30 specifically targets and cleaves ubiquitin chains from proteins on the outer membrane of mitochondria, the energy-producing organelles within cells.

Research has shown that USP30 plays a crucial role in maintaining mitochondrial homeostasis and function. By removing ubiquitin chains from mitochondrial proteins, excessive USP30 activity prevents the degradation of damaged or dysfunctional mitochondria through the process of mitophagy, which is a specialized form of autophagy that eliminates defective mitochondria.

The dysregulation of USP30 has been implicated in several neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. Parkinson’s disease is characterized by the progressive loss of dopaminergic neurons in the brain, leading to motor symptoms such as tremors, rigidity, and bradykinesia. Studies have shown that USP30 inhibition or genetic knockout can enhance mitophagy and protect against the accumulation of damaged mitochondria and neuronal degeneration in cellular and animal models of Parkinson’s disease. Inhibition of USP30 has also been shown to improve mitochondrial function and reduce neurotoxicity in models of other neurodegenerative disorders, such as Huntington’s disease and Alzheimer’s disease.

Given the potential therapeutic implications, USP30 has emerged as a promising target for the development of novel treatments for neurodegenerative disorders. Several small-molecule inhibitors of USP30 have been identified and are being investigated for their potential efficacy in preclinical and early clinical studies. However, it’s important to note that the field of USP30 research is still evolving, and further studies are needed to fully understand its role in neurodegeneration and to evaluate the safety and effectiveness of USP30-targeted therapies in human patients.