Ubiquitin Carboxyl-Terminal Hydrolase 14 (USP14) belongs to the ubiquitin-specific processing (USP) family which is a deubiquitinating enzyme (DUB) with His and Cys domains. USP14 located in the cytoplasm is a proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins. USP14 acts also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1. In addition, USP14 is indispensable for synaptic development and function at neuromuscular junctions, required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis.