TXNDC12 (thioredoxin domain containing 12) is an endoplasmic reticulum (ER) protein with protein-disulfide reductase activity that functions as a thiol-disulfide oxidase to promote disulfide bond formation in client proteins. Beyond its canonical redox function, TXNDC12 has emerged as a multifunctional oncogenic protein with diverse roles across multiple cancer types. In head and neck squamous cell carcinoma, elevated TXNDC12 expression associates with adverse outcomes and cisplatin resistance by stabilizing c-Myc protein through USP5-mediated interactions, with METTL1 enhancing TXNDC12 mRNA stability via m7G-dependent mechanisms 1. In gliomas, TXNDC12 knockdown promotes ferroptosis by modulating SLC7A11 expression, suggesting therapeutic potential 2. TXNDC12 promotes hepatocellular carcinoma metastasis via β-catenin activation and EMT induction 3, and elevated expression in gliomas correlates with poor prognosis and altered immune infiltration 4. Beyond oncology, Mendelian randomization analysis identified TXNDC12 as a causal risk factor for anorexia nervosa, potentially through dopamine reward system regulation 5. Additionally, TXNDC12 has been implicated in autism spectrum disorder pathogenesis through disulfidptosis mechanisms 6 and rheumatoid arthritis fibroblast invasiveness 7. These findings indicate TXNDC12 functions as a context-dependent regulator of cellular processes including protein stability, redox homeostasis, and cell fate determination.