Mutant N-terminal huntingtin (Htt) protein resulting from Huntington's disease 
(HD) with expanded polyglutamine accumulates and forms aggregates in vulnerable 
neurons. Both ubiquitin proteasomal and autophagic pathways contribute to the 
degradation of mutant Htt. Here, we focus on the involvement of 
chaperone-mediated autophagy (CMA), a selective form of autophagy in the 
clearance of Htt. Selective catabolism in CMA is conferred by the presence of a 
KFERQ-like targeting motif in the substrates, by which molecular chaperones 
recognize the hydrophobic surfaces of the misfolded substrates, and transfer 
them to the lysosomal membrane protein type-2A, LAMP-2A. The substrates are 
taken into the lysosomes through LAMP-2A and are rapidly degraded by the 
lysosomal enzymes. Taken together, we summarize the recent evidence to elucidate 
that Htt is also a potential substrate of CMA. We propose that the manipulation 
of CMA could be a therapeutic strategy for HD.