Protein disulfide-isomerase A6 (PDIA6)

Protein disulfide-isomerase A6 (PDIA6) is an endoplasmic reticulum-resident oxidoreductase and molecular chaperone that catalyzes the formation, breakage, and rearrangement of disulfide bonds in nascent and misfolded proteins, ensuring correct protein folding and preventing aggregation within the secretory pathway. PDIA6 plays specialized roles in maintaining ER homeostasis, particularly through regulation of ER stress responses and the unfolded protein response (UPR) by interacting with key signaling proteins such as IRE1. It also supports neuronal repair and regeneration after spinal cord injury, in part by physically interacting with and modulating the function of spastin, a microtubule-severing protein crucial for axonal outgrowth and neuron recovery. Dysregulation or inhibition of PDIA6 activity has been implicated in neurodegenerative disease, ER stress-induced cell death, and inflammation. The PDI family, including PDIA6, is considered a potential therapeutic target, but selective PDIA6 drugs and validated biomarkers are not well established in clinical practice.

Other names

ER protein 5ERp5P5TXNDC7Endoplasmic reticulum protein 5Protein disulfide isomerase P5Thioredoxin domain-containing protein 7Protein disulfide isomerase-related proteinEpididymis secretory sperm binding protein

Inhibition of enzymatic activity (via active-site binding or redox-modifying agents) to disrupt disulfide bond formation/folding and prevent chaperone activity. Reduction of ER stress and modulation of unfolded protein response signaling may be targeted for neuroprotective or anti-inflammatory effects.