Human Ubiquitin Carboxyl Terminal Hydrolase L1 (UCHL1) Protein

Background

UCHL1 is a deubiquitinating enzyme that cleaves ubiquitin from protein substrates, playing a pivotal role in the ubiquitin-proteasome system (UPS). UCHL1 is highly expressed in neurons and is crucial for maintaining protein homeostasis, axonal transport, and synaptic function. It regulates the degradation of misfolded proteins, ensuring neuronal survival and preventing neurotoxicity. Mutations in UCHL1 are linked to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease due to impaired protein turnover and accumulation of toxic aggregates. It also has oncogenic and tumor-suppressive roles depending on the cellular context, regulating cell cycle progression and apoptosis. Knockout studies in mice show progressive neurodegeneration, motor dysfunction, and impaired synaptic activity, highlighting UCHL1’s critical role in neuronal maintenance, proteostasis, and neuroprotection.