Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) (UCHL1)

Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), also known as PGP 9.5, is a highly abundant neuronal enzyme that plays a critical role in the ubiquitin-proteasome system by recycling ubiquitin from degraded proteins (UniProt: P09936). It functions primarily as a deubiquitinating enzyme but can also exhibit ubiquitin ligase activity when dimerized, contributing to the maintenance of the free ubiquitin pool necessary for cellular homeostasis (PubMed: 12446785). Mutations in the UCHL1 gene, such as the I93M variant, are linked to familial Parkinson's disease, while its downregulation is observed in Alzheimer's disease (PubMed: 9771709). Conversely, UCHL1 is frequently overexpressed in various cancers, including lung and colorectal carcinomas, where it promotes tumor progression by stabilizing oncogenic signaling pathways (PubMed: 23603114). As a therapeutic target, small molecule inhibitors are being explored to treat malignancies, while its presence in the blood serves as a clinically validated biomarker for traumatic brain injury (FDA News Release, 2018).

Other names

PGP 9.5Protein gene product 9.5PARK5Ubiquitin C-terminal hydrolase L1Neuron-specific protein PGP9.5

Inhibition of deubiquitinating activity to modulate protein stability and ubiquitin recycling.