Protein disulfide-isomerase A4 (PDIA4)

PDIA4 is a protein disulfide-isomerase belonging to the thioredoxin superfamily, functioning in the endoplasmic reticulum to catalyze protein disulfide bond formation and isomerization (UniProt: P13667). At 645 amino acids and approximately 73 kDa, PDIA4 plays a role in protein folding and quality control within the secretory pathway.

PDIA4 localizes to the endoplasmic reticulum and is involved in oxidative protein folding and the unfolded protein response. These processes are central to cellular stress responses and proteostasis maintenance in neurons and other tissues throughout the body (UniProt: P13667).

In Alzheimer's Disease, PDIA4 shows increased abundance in post-mortem AD brain tissue relative to age-matched controls, with a mean log2 fold-change of +0.54 across detected fractions (Chaparral AD proteomics). This upregulation was detected via TMT-labeled quantitative proteomics across multiple subcellular fractions, suggesting potential involvement in ER-mediated stress responses or compensatory protein-folding mechanisms associated with neurodegeneration (ad:direction:up).