Gpx7, a member of the glutathione peroxidase (GPx) family, lacks typical GPx activity. It functions as a stress sensor/transmitter, shuttling disulfide bonds to transfer signals to interacting proteins in response to various stresses. It is a conserved endoplasmic reticulum (ER) retention protein, and is involved in maintaining redox homeostasis and protein folding in the ER [2,4,8].

In bone marrow mesenchymal stem cells (BMSCs), Gpx7 deficiency reduces osteogenesis and increases adipogenesis. This osteogenic defect can be alleviated by an ER stress antagonist, indicating that Gpx7-deficient-induced ER stress, rather than enhanced ROS, inhibits osteogenesis. The mTOR signalling pathway is down-regulated during osteogenic differentiation in Gpx7-deficient conditions, which can be rescued by relieving ER stress. This suggests Gpx7 may protect against osteoporotic deficits through the ER stress and mTOR pathway interplay [1].

In non-alcoholic steatohepatitis (NASH), knockdown of Gpx7 in relevant cells elevates pro-fibrotic and pro-inflammatory genes and collagen synthesis, while its overexpression suppresses ROS production and reduces these gene expressions. NASH fibrosis in mice is accelerated by Gpx7 knockdown [3].

In chondrocytes, GPX7 level decreases in response to IL-1β treatment, and its overexpression suppresses cellular inflammation, extracellular matrix degradation, apoptosis and ferroptosis [5].

In glioma, GPX7 silencing enhances ferroptosis-related oxidative stress and sensitizes glioma to erastin-induced ferroptosis. High expression of GPX7 is correlated with adverse outcomes in glioma [6].

In papillary thyroid carcinoma (PTC), knockdown of GPX7 decreases cell proliferation and increases apoptosis, indicating high expression of GPX7 promotes PTC growth [7].

In conclusion, Gpx7 plays crucial roles in multiple biological processes and disease conditions. Through gene-knockout-based research, it has been revealed that Gpx7 is involved in osteogenesis, adipogenesis, NASH fibrosis, chondrocyte inflammation and matrix degradation, ferroptosis in glioma, and the growth of papillary thyroid carcinoma. These findings contribute to understanding the mechanisms of these diseases and may provide potential therapeutic targets.