Ubiquitin (Ub) is a highly conserved protein found ubiquitously in eukaryotic organisms. 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 processing protease 16 (USP16) is a member of this family. USP16 activity is cell cycle regulated via phosphorylation and participates in cell cycle control by influencing mitotic chromosome condensation and histone 2A (H2A) deubiquitination.