Deubiquitinating enzyme that hydrolyzes ubiquitin moieties conjugated to substrates and thus, functions to process newly synthesized Ubiquitin, to recycle ubiquitin molecules or to edit polyubiquitin chains and prevents proteasomal degradation of substrates. Hydrolyzes both 'Lys-48'- and 'Lys-63'-linked tetraubiquitin chains (By similarity). The muscle-specific isoform (USP25m) may have a role in the regulation of muscular differentiation and function. Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). Homodimer or oligomer (By similarity). Interacts with ACTA1 (via its C-terminus); the interaction occurs for all isoforms but is strongest for isoform USP25m in muscle differentiating cells. Interacts (isoform USP25m only) with MYBPC1; the interaction prevents proteasomal degradation of MYBPC1. Interacts (isoform USP25m only) with FLNC (via filament repeats 17-18, 20-21 and 24). Interacts with GAPDH. Interacts with SUMO3; the interaction sumoylates efficiently USP25. Interacts with SUMO2; the interaction sumoylates efficiently USP25. Interacts with SUMO1; the interaction only weakly sumoylates USP25. Interacts with SYK; phosphorylates USP25 and regulates USP25 intracellular levels (By similarity). The longer muscle-specific isoform (USP25m) Some transient punctuate nuclear location in myotubes during myocyte development. A longer muscle-specific isoform, USP25m, also exists. Highly expressed in testis especially in primary and secondary spematocytes and in immature spermatids. Also found in brain, skeletal muscle, liver and heart. At 13.5 dpc and 16.5 dpc, expression in the brain correlates with the proliferate ventricular zone and post-mitotic neurons of the intermediate zone, particularly in the forebrain. More marked expression at 16.5 dpc in the telencephalic septum and in the pallium. In myocytes, expressed throughout differentiation of myotubes. Induced by type I interferons (IFNA and IFNB1) produced in response to lipopolysaccharide (LPS) and viral infection (HIV-1 and SeV viruses) (at protein level). Acetylated. Sumoylation impairs binding to and hydrolysis of ubiquitin chains. Sumoylated preferentially with SUMO2 or SUMO3. Desumoylated by SENP1. Regulated by ubiquitination on the same residue (By similarity). Preferentially monoubiquitinated but can also be polyubiquitinated. Autodeubiquitinated. Ubiquitination activates the enzymatic activity either by preventing sumoylation or by allowing novel interactions (By similarity). Phosphorylation in the C-terminal by SYK regulates USP25 cellular levels. Belongs to the peptidase C19 family.