Ubiquitin carboxyl-terminal hydrolase 40 (USP40)

Ubiquitin carboxyl-terminal hydrolase 40 (USP40) is a member of the ubiquitin-specific protease family, acting as a cysteine protease that removes ubiquitin moieties from protein substrates, thereby regulating their stability and degradation. Although USP40 is a poorly characterized deubiquitinating enzyme compared to other USPs, recent studies reveal an important role in protecting vascular endothelial integrity and limiting inflammation by deubiquitinating and inactivating heat shock protein 90β, which mediates cytoskeletal and inflammatory pathways. Loss of USP40 function leads to increased susceptibility to acute lung injury and vascular leakage. Dysregulation of USP40 has been linked to late-onset Parkinson disease, indicating relevance in neurodegenerative conditions. While no drugs targeting USP40 are currently known, its role in deubiquitination, protein homeostasis, and inflammation identifies it as a potential therapeutic target in vascular and neurodegenerative diseases[2][5][6][7][10].

Other names

Ubiquitin specific peptidase 40deubiquitinating enzyme 40ubiquitin thioesterase 40ubiquitin-specific-processing protease 40UBP40FLJ10785

Deubiquitination of protein substrates (notably heat shock protein 90β/HSP90β) Regulation of protein degradation by reversing ubiquitination