Proteasome subunit alpha type-4

PSMA4 (proteasome subunit alpha type-4) is a core component of the 20S proteasome complex, essential for ATP-dependent degradation of ubiquitinated proteins and maintenance of cellular protein homeostasis (UniProt: P25789). The protein participates in multiple proteolytic pathways, including removal of misfolded or damaged proteins and generation of MHC class I-presented peptides when associated with regulatory particles such as the 19S and PA28 complexes.

In the context of Alzheimer's Disease, PSMA4 shows ambiguous regulation across subcellular fractions in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.22 (Chaparral AD proteomics). This modest overall downward trend masks differential regulation across the four measured fractions (P2, P3, S2, S3) from TMT-labeled proteomic analysis, suggesting the protein's abundance or localization may vary by cellular compartment in AD pathology rather than showing consistent directional change.