Quality control and fate determination of Hsp90 client proteins

► Small molecule Hsp90 inhibitors promote client protein degradation via the actions of molecular chaperones. ► Hsp90 can promote degradation as well as protect against degradation of misfolded proteins. ► Several ubiquitin ligases in the degradation of Hsp90 client proteins including CHIP, Ubr1 and Cul5. ► Inhibition of Hsp90 can protect against neurodegeneration.