Ggt7, also known as GGTL3 or GGT4, is a member of the gamma-glutamyltransferase gene family. It is involved in multiple biological processes, such as glutathione metabolism [4]. As a SREBP2-dependent target, Ggt7 positively regulates cellular cholesterol levels, affects the expression of cholesterol metabolism genes, and interacts with MYH10 to control LDL-C uptake, playing an important role in cholesterol and lipid homeostasis [5].

In pancreatic cancer, TXNDC12 inhibits ferroptosis in pancreatic adenocarcinoma (PAAD) cells through the GSH/GGT7 axis, promoting tumor development. Knockdown of TXNDC12 led to decreased intracellular GSH content, increased GSSG content, and elevated pro-ferroptosis factors, and these effects could be reversed by overexpression of GGT7 [1].

In gastric cancer, GGT7 is frequently downregulated by promoter methylation. High-expression of GGT7 in adjacent non-tumor tissues is associated with favorable survival. GGT7 inhibits gastric cancer cell growth, G1-S transition, migration, and invasion, and attenuates xenograft tumor growth and lung metastasis in nude mice. It binds directly with RAB7 to induce mitophagy, inhibit ROS, and suppress MAPK cascades [2].

In glioblastoma (GBM), low GGT7 expression is associated with a worse prognosis. Exogenous expression of GGT7 reduces proliferation and anchorage-independent growth, while decreasing its expression increases proliferation and tumor growth in mice, suggesting GGT7 can be a biomarker and therapeutic target for GBM by regulating anti-oxidative damage [3].

In conclusion, Ggt7 is involved in multiple biological functions including glutathione metabolism and cholesterol homeostasis. Its dysregulation is associated with various diseases such as pancreatic cancer, gastric cancer, and glioblastoma. Functional studies, especially those using gene-knockout models, have provided insights into its role in these disease conditions, offering potential directions for biomarker discovery and therapeutic development.