UCH-L1 is a member of a gene family whose products hydrolyze small C-terminal adducts of ubiquitin to generate the ubiquitin monomer. Expression of UCH-L1 is highly specific to neurons and to cells of the diffuse neuroendocrine system and their tumors. UCH-L1 is expressed in brain neurons. Examination of specific brain regions reveals expression in all areas tested, particularly in the substantia nigra. UCH-L1 represents 1 to 2% of total soluble brain protein. Its occurrence in Lewy bodies and its function in the proteasome pathway make it a compelling candidate gene in Parkinson disease. The gene which encodes UCH-L1 maps to human chromosome 4p14. The 230 amino acid human UCH-L3 protein is 54% identical to that of UCH-L1. UCH-L3 is the predominant thiol protease and has high-affinity binding sites for ubiquitin.