The ubiquitin (Ub) pathway involves three sequential enzymatic steps that facilitate the conjugation of Ub and Ub-like molecules to specific protein substrates. Through the use of a wide range of enzymes that can add or remove ubiquitin, the Ub pathway controls many intracellular processes such as signal transduction, transcriptional activation and cell cycle progression. USP21 (ubiquitin specific peptidase 21), also known as USP16 or USP23, is a 565 amino acid protein that belongs to the C19 peptidase family of ubiquitin carboxy-terminal hydrolases. Capable of removing ubiquitin from ubiquitinated proteins, USP21 plays a role in signal transduction and can also remove NEDD8 from NEDD8-conjugated proteins, possibly functioning to influence NEDD8-mediated protein proteolysis. Multiple isoforms of USP21 exist due to alternative splicing events.