Lamp2a acts as a receptor in the lysosomal membrane for substrate proteins of 
chaperone-mediated autophagy. Using antibodies specific for the cytosolic tail 
of lamp2a and others recognizing all lamp2 isoforms, we found that in rat liver 
lamp2a represents 25% of lamp2s in the lysosome. We show that lamp2a levels in 
the lysosomal membrane in rat liver and fibroblasts in culture directly 
correlate with rates of chaperone-mediated autophagy in a variety of 
physiological and pathological conditions. The concentration of other lamp2s in 
the lysosomal membrane show no correlation under the same conditions. 
Furthermore, substrate proteins bind to lamp2a but not to other lamp2s. Four 
positively-charged amino acids uniquely present in the cytosolic tail of lamp2a 
are required for the binding of substrate proteins. Lamp2a also distributes to 
an unique subpopulation of perinuclear lysosomes in cultured fibroblasts in 
response to serum withdrawal, and lamp2a, more than other lamp2s, tends to 
multimerize. These characteristics may be important for lamp2a to act as a 
receptor for chaperone-mediated autophagy.