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Review
. 2025 Jun 16:S1471-4914(25)00117-0.
doi: 10.1016/j.molmed.2025.05.006. Online ahead of print.

OTU deubiquitinases in disease: roles and targeting

Yu Deng  1 , Pengda Liu  2
Affiliations
Review

OTU deubiquitinases in disease: roles and targeting

Yu Deng et al. Trends Mol Med. .

Abstract

Dysregulation of protein homeostasis contributes to many human diseases and is an emerging therapeutic target. Proteasome-mediated degradation requires ubiquitin tagging, a process regulated by E3 ligases and reversed by deubiquitinases (DUBs). Among DUBs, the ovarian tumor protease (OTU) family exhibits poly-ubiquitin linkage-specific activity and regulates diverse cellular processes. OTU dysregulation has been linked to diseases such as cancer, highlighting their potential as drug targets. This review summarizes current knowledge of OTU functions, regulatory mechanisms, and disease associations, as well as therapeutic strategies targeting OTUs. By examining these aspects, we aim to provide insights into the pathophysiological roles of OTUs and support ongoing efforts to develop OTU-targeted therapies for human diseases.

Keywords: OTU-deubiquitinase; pathophysiological function; protein stability; small molecule inhibitors; targeted therapy; ubiquitination.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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