Ubiquitin carboxyl-terminal hydrolase 10

USP10 is a deubiquitinating enzyme that removes conjugated ubiquitin from diverse target proteins, including p53, ribosomal proteins, BECN1, and CFTR (UniProt: Q14694). It functions as a critical regulator of p53 stability in both cytoplasmic and nuclear compartments, particularly in response to DNA damage, and plays a key role in ribosome quality control by preventing degradation of 40S ribosomal subunits during translation stalling. USP10 also negatively regulates stress granule formation and participates in autophagy and immune signaling pathways.

USP10 is expressed across multiple tissues and is involved in p53-dependent DNA damage responses, autophagy regulation, and innate immune responses to viral infection (UniProt: Q14694). The protein interfaces with fundamental cellular stress-response pathways through its interaction with the PIK3C3/VPS34 autophagy complex and through TANK-dependent NF-κB attenuation.

In Alzheimer's disease, USP10 shows reduced abundance in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.21 (Chaparral AD proteomics). This downregulation may impair p53 stabilization and ribosomal protein recycling, potentially contributing to compromised protein quality control and increased cellular stress in AD pathology.