CHAC1, also known as glutathione-specific γ-glutamylcyclotransferase 1, is an essential regulator of oxidative stress and ferroptosis. As a γ-glutamyl cyclotransferase, it degrades glutathione, influencing calcium signaling and mitochondrial function. It is involved in the unfolded protein response pathway and is crucial for maintaining redox balance and regulating cell death pathways [2].

In ischemic stroke, CHAC1 is a key gene in the progress of ferroptosis. miR-760-3p in adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exo) can inhibit CHAC1 expression, and IN administration of anti-CHAC1 ADSC-Exo can improve neurobehavior function and ferroptosis-related outcomes in mice after cerebral ischemia/reperfusion injury [1].

In lung adenocarcinoma, CHAC1 expression is higher in tumor tissues, and its overexpression promotes cell proliferation, migration, invasion, and glycolysis by enhancing the SUMOylation of PKM2 and promoting its nuclear translocation [3].

In thyroid carcinoma, overexpression of CHAC1 promotes cell ferroptosis and enhances radiation sensitivity [4].

In sepsis-induced acute kidney injury, CHAC1 exacerbates ferroptosis and apoptosis in HK-2 cells by promoting oxidative stress [5].

In conclusion, CHAC1 plays a significant role in multiple disease conditions, especially those related to oxidative stress and ferroptosis. Studies on CHAC1 using various models, including in vivo mouse models, have revealed its functions in different biological processes, offering potential therapeutic targets for diseases such as ischemic stroke, lung adenocarcinoma, thyroid carcinoma, and sepsis-induced acute kidney injury.