26S proteasome non-ATPase regulatory subunit 6

PSMD6 (26S proteasome non-ATPase regulatory subunit 6) is a structural component of the 26S proteasome, the ATP-dependent protein degradation machinery responsible for removing ubiquitinated proteins. The protein is essential for maintaining protein homeostasis by targeting misfolded or damaged proteins and regulating proteins whose functions are no longer needed. Through these functions, the proteasome participates in cell cycle progression, apoptosis, and DNA damage repair (UniProt: Q15008).

PSMD6 is part of the ubiquitin-proteasome system, a fundamental cellular quality-control pathway. No intrinsic disease annotations are documented in UniProt for this protein.

In Alzheimer's Disease, PSMD6 is downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC −0.30; Chaparral AD proteomics). This reduction was observed across subcellular fractions in TMT-labeled proteomics analysis, suggesting a decline in proteasomal capacity that may contribute to impaired protein clearance and accumulation of pathogenic proteins characteristic of AD neurodegeneration.