A subset of cytosolic proteins can be selectively degraded in lysosomes through 
chaperone-mediated autophagy. The lysosomal-membrane protein type 2A (LAMP-2A) 
acts as the receptor for the substrates of chaperone-mediated autophagy (CMA), 
which should undergo unfolding before crossing the lysosomal membrane and 
reaching the lumen for degradation. Translocation of substrates is assisted by 
chaperones on both sides of the membrane, but the actual steps involved in this 
process and the characteristics of the translocation complex were, for the most 
part, unknown. We have now found that rather than a stable translocon at the 
lysosomal membrane, CMA substrates bind to monomers of LAMP-2A driving the 
organization of this protein into a high molecular weight multimeric complex 
that mediates translocation. Assembly and disassembly of LAMP-2A into and from 
this complex is dynamic and it is regulated by hsc70 and hsp90, the two 
lysosomal chaperones related to CMA. This work thus unveils a unique mechanism 
of protein translocation across the lysosomal membrane, which involves only 
transient discontinuity of the membrane. The possible advantages of this 
transitory lysosomal translocon are discussed in light of the unique properties 
of the lysosomal compartment.