Thioredoxin domain-containing protein 15 (TXNDC15)

Thioredoxin domain-containing protein 15 (TXNDC15) is an endoplasmic reticulum (ER)-localized, thioredoxin-related transmembrane protein belonging to the protein disulfide isomerase (PDI) family[3][4][5]. It catalyzes the formation, reduction, and isomerization of disulfide bonds, thereby ensuring proper oxidative protein folding and contributing to ER proteostasis[4][5]. TXNDC15 has an atypical thioredoxin domain featuring a non-canonical CRFS active site, making it a “natural trapping mutant” within the PDI family, uniquely engaging in stable mixed disulfide complexes with other proteins[4]. Functionally, TXNDC15 is required for the integrity of the ciliary transition zone, and knockout disrupts assembly of the Meckel syndrome (MKS) module, leading to ciliopathies such as Meckel–Gruber syndrome (MKS)[2][3][4]. Mutations in TXNDC15 are causative for MKS, a severe inherited developmental disorder. While its broader roles in protein folding and redox biology are recognized, recent studies have associated altered expression levels of TXNDC15 with prognosis in glioma and other cancers, suggesting potential but still uncharacterized disease-modulating functions[5]. There are currently no drugs directly targeting TXNDC15, and no established therapeutic safety challenges linked to TXNDC15 inhibition or manipulation in humans.

Other names

C5orf14TMX5FLJ226252310047H23RikMKS14UNQ335PRO534BUGdisulfide isomerase

No characterized pharmacological mechanism of action targeting TXNDC15 directly