Txndc5, also known as endothelial protein-disulfide isomerase (Endo-PDI) and endoplasmic reticulum protein 46 (ERp46), is a member of the protein disulfide isomerase (PDI) family. It can promote the formation and rearrangement of disulfide bonds, ensuring proper protein folding, and has three Trx-like domains that act independently to introduce disulfide bonds rapidly and disorderly. It plays crucial roles in regulating cell proliferation, apoptosis, migration, and antioxidative stress, and is associated with multiple biological processes and diseases [1,4,5,6]. Genetic models, such as KO and CKO mouse models, are valuable for studying its functions.

In renal fibrosis, fibroblast-specific deletion of Txndc5 in a tamoxifen-inducible, fibroblast-specific Txndc5 knockout mouse line mitigated the progression of established kidney fibrosis, suggesting that Txndc5 promotes renal fibrosis by enforcing TGF-β signaling in kidney fibroblasts [2]. In liver fibrosis, HSC-specific deletion of Txndc5 reverted established liver fibrosis in mice, indicating that Txndc5 promotes liver fibrosis through redox-dependent HSC activation, proliferation, and excessive extracellular matrix production [3].

In conclusion, Txndc5 is essential for proper protein folding and has diverse functions in cell regulation. The use of Txndc5 KO/CKO mouse models has revealed its significant role in organ fibrosis, including renal and liver fibrosis, highlighting its potential as a therapeutic target for these diseases.