Gab2, short for Grb2-associated binder 2, is a scaffolding protein that links plasma membrane receptor signaling to downstream effectors [2]. It is essential for major signal transduction pathways like the PI3-K-AKT and extracellular signal-regulated kinase (ERK) signaling pathways, regulating key cellular processes such as growth, differentiation, migration, and apoptosis [2,6].

In the context of diseases, Gab2 has been implicated in multiple conditions. In deep vein thrombosis (DVT), Gab2 facilitates the assembly of the CBM signalosome in endothelial cells, regulating thromboinflammation. Gene silencing of Gab2 reduced IL-1β-induced responses related to thrombosis in vitro, and Gab2 deficiency suppressed thrombosis in mouse models, suggesting its role in DVT pathogenesis [1]. In cancer, Gab2 promotes the growth and migration of acute myeloid leukemia (AML) cells through the SHP2-Erk-CREB signaling pathway, and Gab2 deficiency prevents Flt3-ITD driven AML in vivo, indicating its carcinogenic role in AML [4,5]. In ovarian cancer, high expression of Gab2 is associated with poor prognosis, and it promotes the proliferation, metastasis, and reduces chemosensitivity of ovarian cancer cells through regulating CrkII [3]. Also, in hepatocellular carcinoma, the tumor suppressor Foxd3 negatively regulates Gab2, and their mutual inhibition controls carcinogenesis [7].

In conclusion, Gab2 plays crucial roles in regulating cellular processes through its involvement in key signaling pathways. Gene knockout or knockdown studies, especially in mouse models, have revealed its significant contributions to diseases such as DVT and various cancers. Understanding Gab2's functions provides potential therapeutic targets for these disease areas.