26S proteasome non-ATPase regulatory subunit 1

PSMD1 encodes a non-ATPase regulatory subunit of the 26S proteasome, a multiprotein complex essential for ATP-dependent degradation of ubiquitinated proteins (UniProt: Q99460). This component is critical for protein homeostasis, participating in removal of misfolded or damaged proteins and supporting cellular processes including cell cycle progression, apoptosis, and DNA damage repair (UniProt: Q99460).

The proteasome pathway is central to neuronal protein quality control and has been implicated in neurodegenerative disease pathology. In Alzheimer's disease, proteasomal dysfunction may contribute to accumulation of pathogenic protein aggregates including amyloid-β and tau.

PSMD1 is downregulated in post-mortem Alzheimer's disease brain tissue compared to age-matched controls (mean log2FC: −0.2916; Chaparral AD proteomics), based on quantitative proteomics analysis of subcellular fractions from human brain. This reduction in proteasomal subunit abundance may compromise protein clearance capacity and contribute to the pathological protein accumulation characteristic of AD.