Autosomal recessive juvenile parkinsonism (AR-JP) is caused by mutations of the 
parkin gene. Parkin is an E3 ubiquitin ligase that specifically recognizes its 
substrate protein, promoting its ubiquitination and subsequent degradation. 
Accordingly, we hypothesized that AR-JP may be caused by accumulation of an 
unidentified neurotoxic protein, which is a substrate of parkin. Based on this 
hypothesis, we cloned parkin-binding protein using a yeast two-hybrid system and 
identified a putative G protein-coupled receptor protein,which we named the Pael 
receptor (Pael-R). When overexpressed in cells, this receptor became unfolded, 
insoluble, and ubiquitinated. Accumulation of the insoluble Pael-R subsequently 
led to endoplasmic reticulum (ER) stress-induced cell death. Parkin specifically 
ubiquitinates the unfolded Pael-R and promotes its degradation, resulting in 
suppression of cell death induced by the accumulation of unfolded Pael-R. 
Moreover, insoluble Pael-R accumulates in the brains of AR-JP patients. It is 
highly expressed by the dopaminergic neurons of the substantia nigra, strongly 
suggesting that accumulation of unfolded Pael-R may lead to selective death of 
dopaminergic neurons in AR-JP.Recently, we identified Hsp70 and its co-chaperone 
CHIP as novel parkin-binding partners. We found that CHIP enhanced 
parkinmediated ubiquitination of Pael-R. In concert with Hsp70, CHIP also 
enhanced the ability of parkin to inhibit cell death induced by Pael-R, 
indicating that CHIP and Hsp70 are both co-factors of parkin.