TXNL1 in redox and protein quality control: mechanisms and disease relevance

Abstract

TXNL1 (thioredoxin-like protein 1), a member of the thioredoxin superfamily, integrates thioredoxin oxidoreductase activity with molecular chaperone function. Through its N-terminal TRX domain and C-terminal PITH domain, TXNL1 not only helps maintain cellular redox homeostasis but also prevents toxic aggregation of oxidatively damaged proteins. Consequently, TXNL1 acts as a critical buffer in the cellular defense against oxidative stress and in protein quality control. TXNL1 is widely expressed across diverse tissues, and its dysregulation is closely associated with multiple pathological conditions, including chemotherapy resistance in gastric cancer, poor prognosis in colorectal cancer, arsenic-induced malignant transformation of bronchial epithelial cells, and ischemic as well as traumatic injuries of the central nervous system. TXNL1 undergoes degradation through both canonical ubiquitin-dependent and ubiquitin-independent mechanisms. This review summarizes the discovery, molecular architecture, expression patterns, physiological functions, and disease-related research progress of TXNL1, and discusses its potential clinical applications as a biomarker and therapeutic target.