Intracellular proteins are targeted for proteolytic degradation in the lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) acts as the constitutive chaperone that binds a KFERQ-domain containing substrate in the cytosol and translocates to lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, Hspa8 is released and Heat shock protein HSP90 binds to the lysosomal luminal end of LAMP2a. The LAMP2a complex then multimerizes and stabilizes. Now, the substrate unfolds and binds to HSPA8 in the lysosomal lumen (Agarraberes FA et al. 1997, Cuervo AM et al. 1997). Subsequently, the substrate is internalized and degraded in the lumen. Experiments confirming this interaction were performed in rats.