26S proteasome non-ATPase regulatory subunit 3

PSMD3 (26S proteasome non-ATPase regulatory subunit 3) is a component of the 26S proteasome, the ATP-dependent protein degradation machinery (UniProt: O43242). It functions as part of a multiprotein complex essential for removing ubiquitinated, misfolded, or damaged proteins, thereby maintaining cellular protein homeostasis. The proteasome participates in critical processes including cell cycle progression, apoptosis, and DNA repair.

PSMD3 is a structural subunit of the proteasome, which is widely expressed across tissues and is fundamental to cellular quality control pathways. No primary disease associations are documented in UniProt for this protein.

PSMD3 is downregulated in Alzheimer's disease brain tissue compared to age-matched controls (mean log2 fold-change −0.15; Chaparral AD proteomics). This reduction was identified in a study of human post-mortem AD brain using TMT-labeled, data-dependent acquisition proteomics across four subcellular fractions. The modest downregulation suggests potential impairment of proteasomal degradation capacity in AD pathology, which may contribute to accumulation of disease-relevant protein aggregates.