Ubiquitin C-terminal hydrolase L1 (UCH-L1) is expressed abundantly in neurons 
and has been reported to be a major target of oxidative/carbonyl damage 
associated with sporadic Parkinson's disease (PD). The I93M mutation in UCH-L1 
is also associated with familial PD. We recently reported that UCH-L1 physically 
interacts with LAMP-2A, the lysosomal receptor for chaperone-mediated autophagy 
(CMA), and Hsc70 and Hsp90, both of which can function as components of the CMA 
pathway. We found that the levels of these interactions were aberrantly 
increased by the I93M mutation, and that expression of I93M UCH-L1 in cells 
induced the CMA inhibition-associated increase in the amount of alpha-synuclein, 
a risk factor for PD. The interactions of UCH-L1 with LAMP-2A, Hsc70 and Hsp90 
were also abnormally enhanced by carbonyl modification of UCH-L1. We propose 
that aberrant interactions of UCH-L1 variants with CMA machinery, at least 
partly, underlie the pathogenesis of I93M UCH-L1-associated PD, and possibly of 
sporadic PD. Our findings may provide novel insights into the links between 
familial and sporadic PD.