TXNDC5 (thioredoxin domain containing 5) is a protein disulfide isomerase (PDI) family member localized to the endoplasmic reticulum (ER) lumen through a KDEL retention signal 1. Its primary function is regulating disulfide bond formation, isomerization, and degradation in target proteins, thereby controlling protein folding, conformation, and stability 2. TXNDC5 possesses three Trx-like domains enabling rapid disulfide bond introduction and rearrangement 2. The protein exhibits molecular chaperone activity and anti-oxidative stress functions 3. Abnormally elevated TXNDC5 expression correlates with multiple pathological conditions. In cancer, increased TXNDC5 promotes cell proliferation and inhibits apoptosis across cervical, gastric, and colorectal carcinomas 3. TXNDC5 associates with rheumatoid arthritis, diabetes, hepatic steatosis, and vitiligo, with TXNDC5 gene polymorphisms linked to vitiligo susceptibility 4. In vascular calcification, TXNDC5 upregulation promotes osteogenic transdifferentiation through Runx2-dependent mechanisms, which SGLT2 inhibitors can suppress 5. In thyroid eye disease, TGF-β1 induces TXNDC5 upregulation, driving myofibroblast transdifferentiation; TXNDC5 knockdown attenuates this fibrotic response 6. Elevated plasma TXNDC5 serves as a biomarker for acute respiratory distress syndrome post-cardiopulmonary bypass 7. These findings suggest TXNDC5 as a promising therapeutic target across inflammatory, fibrotic, and malignant diseases.