Gigyf2, also known as Grb10-interacting GYF protein 2, is an RNA-binding protein involved in multiple biological processes. It plays roles in regulating translation initiation, with its function being relevant to ribosome-associated quality control pathways. It can inhibit the translation initiation of defective messenger RNAs, protecting cells from the toxicity of incomplete protein products [2]. It also participates in various signaling pathways, such as the mTORC1-S6K1 signaling cascade, and is associated with processes like cell senescence, endothelial function, and insulin resistance [1,3].

In endothelial cells, silencing Gigyf2 in senescent cells suppresses eNOS-uncoupling, senescence, and endothelial dysfunction. Conversely, overexpressing it in non-senescent cells promotes these processes and activates the mTORC1-S6K1 pathway. In mice, Gigyf2flox/flox Cdh-Cre+ mice are protected from aging-associated vascular endothelium-dependent relaxation and arterial stiffness [1]. In hepatic cells, silencing Gigyf2 ameliorates palmitic acid-induced insulin resistance, while its overexpression promotes insulin resistance through the up-regulation of STAU1/PTEN and inactivation of the PI3K/AKT pathway. In vivo, Gigyf2 knockdown in mice alleviates high-fat diet-induced glucose intolerance and insulin resistance [3].

In conclusion, Gigyf2 is a crucial regulator in processes such as cell senescence, endothelial function, and insulin resistance. Studies using gene-modified mouse models, like knockout (KO) or conditional knockout (CKO) models, have revealed its role in these processes and related diseases, providing potential therapeutic targets for conditions like vascular aging, aging-related cardiovascular diseases, and obesity-related metabolic diseases [1,3].