USP14 (Ubiquitin Specific Protease 14) is the human homolog of the yeast Ubp6 protein and is member a of the family of thiol proteases involved in the hydrolysis of ubiquitin C-terminal protein derivatives. It has been reported to have a low-affinity association with the proteasome (PA700, 19S cap particle), which increases its basal enzyme activity. The primary physiological role of USP14 may be the release of ubiquitin from proteosome-bound conjugates. In vitro, the enzyme has a low affinity for ubiquitin and is unable to disassemble poly-ubiquitin protein conjugates. Mice homozygous for spontaneous USP14 mutations develop ataxia and this enzyme may play an important role in regulating synaptic activity in mammals. USP14 may also have a role in colorectal cancer metastases, possibly controlling the fate of proteins that regulate tumor invasion. Accession # NP_005142.