Grb2, also known as Growth factor receptor-bound protein 2, is a 25-kDa adaptor protein. It contains a central Src homology type 2 (SH2) domain flanked by two Src homology type 3 (SH3) domains. Grb2 is pivotal in multiple cellular functions, acting as an intermediate in signal transduction pathways. It links activated cell-surface receptors to downstream targets, regulating cell growth, proliferation, metabolism, and is involved in pathways like RAS-ERK1/2 and AKT signaling [3,4].

In a syngeneic mouse metastatic ovarian cancer model, GRB2 depletion combined with PARP inhibitor treatment reduced tumor burden and increased survival, as GRB2 depletion releases DNA fragments from stalled forks to activate the cGAS-STING pathway. This shows GRB2's role in protecting DNA at stalled replication forks in the BRCA2-RAD51-MRE11 axis [1]. In ovo studies in a CAM model, GRB2 knockdown and overexpression of loss-of-function mutants compromised tumor growth, correlating with differential autophagy activity, indicating GRB2's role in regulating autophagy through BECN1 interaction [2]. In BLM-induced skin fibrosis mice, GRB2 knockdown alleviated skin fibrosis and endothelial cell apoptosis, suggesting GRB2 as a potential target for systemic sclerosis [5].

In conclusion, Grb2 is crucial for multiple cellular functions and signaling pathways. Studies using mouse models, such as the metastatic ovarian cancer, in ovo CAM, and BLM-induced skin fibrosis mouse models, have revealed its significance in cancer, autophagy, and skin fibrosis. These findings provide potential therapeutic targets for related diseases.