# Thioredoxin Domain Containing 5 (TXNDC5): Friend or Foe?

## TL;DR

TXNDC5 is a protein with dual roles in disease, acting as a tumor promoter in cancer but protecting normal cells from stress.

## Contribution

The paper reviews TXNDC5's dual role in disease and highlights its potential as a biomarker or pharmacological target.

## Key findings

- TXNDC5 is highly expressed in endothelial cells, fibroblasts, and cancerous tissues.
- TXNDC5 promotes tumor cell survival against apoptosis but protects normal cells from stress.
- TXNDC5 is associated with multiple diseases and has both oncogenic and tumor-suppressive features.

## Abstract

This review focuses on the thioredoxin domain containing 5 (TXNDC5), also known as endoplasmic reticulum protein 46 (ERp46), a member of the protein disulfide isomerase (PDI) family with a dual role in multiple diseases. TXNDC5 is highly expressed in endothelial cells, fibroblasts, pancreatic β-cells, liver cells, and hypoxic tissues, such as cancer endothelial cells and atherosclerotic plaques. TXNDC5 plays a crucial role in regulating cell proliferation, apoptosis, migration, and antioxidative stress. Its potential significance in cancer warrants further investigation, given the altered and highly adaptable metabolism of tumor cells. It has been reported that both high and low levels of TXNDC5 expression are associated with multiple diseases, such as arthritis, cancer, diabetes, brain diseases, and infections, as well as worse prognoses. TXNDC5 has been attributed to both oncogenic and tumor-suppressive features. It has been concluded that in cancer, TXNDC5 acts as a foe and responds to metabolic and cellular stress signals to promote the survival of tumor cells against apoptosis. Conversely, in normal cells, TXNDC5 acts as a friend to safeguard cells against oxidative and endoplasmic reticulum stress. Therefore, TXNDC5 could serve as a viable biomarker or even a potential pharmacological target.