Ubiquitin carboxyl-terminal hydrolase L1 (UCH–L1), also known as PGP 9.5, is a neuronal and neuroendocrine-specific protein that plays a role in proteosomal protein degradation, which is critical for neuronal health. UCH-L1 is also involved in p27kip1 degradation through its interaction and nuclear translocation with JAB1. UCH-L1 expression is specifically associated with non small-cell lung cancer development and it is found in serum of patients with lung cancer, indicating that it may be important in lung cancer screening and diagnosis UCH-L1 may also be a useful marker for invasive colorectal cancer. Mutations in the alpha-synuclein and Uch-L1 genes cause autosomal dominant Parkinson’s disease (PD). Derangements in the ubiquitin proteasomal pathway may play important roles in the demise of dopamine neurons in PD.