Deubiquitinase that plays a role in the regulation of several processes such as maintenance of synaptic function, cardiac function, inflammatory response or osteoclastogenesis. Abrogates the ubiquitination of multiple proteins including WWTR1/TAZ, EGFR, HIF1A and beta-site amyloid precursor protein cleaving enzyme 1/BACE1. In addition, recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin to maintain a stable pool of monoubiquitin that is a key requirement for the ubiquitin-proteasome and the autophagy-lysosome pathways. Regulates amyloid precursor protein/APP processing by promoting BACE1 degradation resulting in decreased amyloid beta production. Plays a role in the immune response by regulating the ability of MHC I molecules to reach cross-presentation compartments competent for generating Ag-MHC I complexes. Mediates the 'Lys-48'-linked deubiquitination of the transcriptional coactivator WWTR1/TAZ leading to its stabilization and inhibition of osteoclastogenesis. Deubiquitinates and stabilizes epidermal growth factor receptor EGFR to prevent its degradation and to activate its downstream mediators. Modulates oxidative activity in skeletal muscle by regulating key mitochondrial oxidative proteins. Enhances the activity of hypoxia-inducible factor 1-alpha/HIF1A by abrogateing its VHL E3 ligase-mediated ubiquitination and consequently inhibiting its degradation.