The conjugation of ubiquitin to proteins is an important means to regulate protein activity for many cellular processes by tagging them for degradation. Removal of Ub can rescue proteins from degradation. This is accomplished by the ubiquitin-specific processing protease (UBP) family of enzymes. Ubiquitin specific peptidase 20 (USP20) is a UBP and is also called von-Hippel-Lindau protein (pVHL) interacting deubiquitinating enzyme 2 (VDU2). pVHL is an E3 ubiquitin-ligase that ubiquitinates hypoxia-inducible factor (HIF)-1alpha. USP20/VDU2 functions to specifically deubiquitinate HIF-1alpha to increase expression of HIF-1alpha regulated genes.