Proteasome 26S subunit, non-ATPase 6 (PSMD6)

Proteasome 26S subunit, non-ATPase 6 (PSMD6), also known as Rpn7, is a non-catalytic component of the 19S regulatory particle of the 26S proteasome (Wikipedia, 2025; UniProt, 2024). The 26S proteasome is a large multi-protein complex essential for the ubiquitin-dependent degradation of misfolded or damaged proteins, thereby maintaining cellular protein homeostasis (GeneCards, 2024). PSMD6 specifically functions within the lid subcomplex of the 19S particle, contributing to proteasome assembly and the recognition of ubiquitinated substrates (Open Targets, 2024). In the context of disease, PSMD6 is frequently overexpressed in various malignancies, such as hepatocellular carcinoma and multiple myeloma, where it promotes cell proliferation and survival (NIH, 2024; ResearchGate, 2025). Its high expression is often associated with poor clinical outcomes and resistance to standard proteasome inhibitors (NIH, 2024). While current clinical inhibitors like bortezomib primarily target the catalytic 20S core, PSMD6 is considered an emerging therapeutic target for the development of next-generation inhibitors or gene-silencing therapies (NIH, 2024; MDPI, 2023). Additionally, its role in protein quality control links it to the pathogenesis of neurodegenerative diseases like Parkinson's and Alzheimer's (Wikipedia, 2025). Targeting PSMD6 or its interactions within the proteasome complex offers a potential strategy to overcome resistance in cancer treatment (NIH, 2024).

Other names

Rpn7p44S10S10KIAA0107PFAAP4SGA-113M26S proteasome regulatory subunit S1026S proteasome regulatory subunit RPN7

Inhibition of the 26S proteasome complex, which prevents the degradation of polyubiquitinated proteins, thereby inducing proteotoxic stress and apoptosis in susceptible cells.