Ubiquitin specific peptidase 48 (USP48)

Ubiquitin specific peptidase 48 (USP48; also known as USP31) is a member of the ubiquitin-specific protease (USP) family of deubiquitinating enzymes that specifically hydrolyze the peptide bond at the C-terminal glycine of ubiquitin and remove ubiquitin moieties from target proteins. USP48 is predominantly localized in neuronal nuclei due to a conserved nuclear localization signal, where it tightly regulates synaptic development and plasticity by interacting with and deubiquitinating key signaling molecules such as NF-κB subunit p65. This stabilization increases NF-κB transcriptional activity and affects the expression of genes implicated in synapse pruning. USP48 also plays a regulatory role in cell cycle progression by stabilizing proteins like Aurora B kinase, in DNA damage response as a histone H2A deubiquitinase counteracting BRCA1-mediated chromatin modification, and in modulating apoptosis and photoreceptor homeostasis. Mutations or dysregulation of USP48 are causally linked to endocrine tumors (notably Cushing’s disease), cancer, Fanconi anemia, and neurodevelopmental as well as neurodegenerative diseases. USP48’s activity is essential for genomic maintenance, proper neural circuit assembly, and immune response regulation, positioning it as a potentially significant therapeutic target in oncology, neurobiology, and inflammation.

Other names

Ubiquitin carboxyl-terminal hydrolase 48USP31FLJ23277FLJ11328FLJ20103FLJ23054MGC14879Deubiquitinating enzyme 48Ubiquitin thioesterase 48Ubiquitin-specific-processing protease 48DFNA85RAP1GA1Ubiquitin-specific protease 48Ubiquitin specific protease 31Ubiquitin thiolesterase 48

Small molecule inhibition of deubiquitinating activity (theoretical; various DUB inhibitors exist but none reported specific for USP48) Modulation of downstream protein stability or signaling (by inhibition/activation of USP48)