Itgb4, short for Integrin beta 4, is a transmembrane protein acting as a mechanosensor, mediating bidirectional information exchange between intracellular and extracellular matrices. It plays a crucial role in cell adhesion, migration, and signaling, and is involved in pathways such as those related to focal adhesion kinase (FAK), protein kinase B (AKT), and matrix metalloproteinases (MMPs) [2].

In triple negative breast cancer, Itgb4-overexpressing cancer cells transfer Itgb4 proteins to cancer-associated fibroblasts (CAFs) via exosomes, inducing BNIP3L-dependent mitophagy and lactate production in CAFs, which in turn promotes breast cancer cell proliferation, epithelial-to-mesenchymal transition, and invasion [1]. In airway epithelial cells, Itgb4 deficiency enhances asthma susceptibility and airway remodeling through the SHP2/JNK/c-Jun/FGF2 signaling pathway, and also aggravates RSV infection and increases HDM sensitivity by down-regulating IFN-λ through the EGFR/IRF-1 pathway [3,4]. Additionally, in esophageal carcinoma, NEDD4L mediates Itgb4 ubiquitination and degradation to suppress carcinoma progression [5].

In conclusion, Itgb4 is essential for cell adhesion, migration, and signaling. Its dysregulation is implicated in multiple diseases, especially various cancers and airway-related diseases. Studies using gene knockout or conditional knockout mouse models have been instrumental in revealing its role in these disease conditions, providing potential therapeutic targets for treatment.