Different mechanisms target intracellular components for their degradation into 
lysosomes through what is known as autophagy. In mammals, three main forms of 
autophagy have been described: macroautophagy, microautophagy, and 
chaperone-mediated autophagy (CMA). CMA is the only autophagic pathway that 
allows selective degradation of soluble proteins in lysosomes. In contrast to 
the other mammalian forms of autophagy, CMA does not require vesicle formation 
or major changes in the lysosomal membrane. Instead, substrate proteins directly 
cross the lysosomal membrane to reach the lumen, where they are rapidly 
degraded. The substrate proteins are targeted to the lysosomal membrane by 
recognition of a targeting motif (a KFERQ-like motif), by a chaperone complex, 
consisting of hsc70 and its cochaperones, in the cytoplasm. Once at the 
lysosomal membrane, the protein interacts with a lysosomal receptor for this 
pathway, lysosomal associated membrane protein type 2A (LAMP-2A), and it is 
translocated across the membrane into the lysosomal lumen assisted by a lysosome 
resident chaperone. These two characteristics--selectivity and direct substrate 
translocation--determine the particular role of CMA in different physiological 
and pathological conditions. In this chapter, we cover current findings on the 
molecular mechanisms for CMA and the possible pathophysiological relevance of 
this selective lysosomal degradation.