TOB1, also known as Transducer of ERBB2.1, is a tumor-suppressor protein. It negatively regulates the receptor tyrosine-kinase ERBB2. TOB1 is involved in multiple biological processes such as cell proliferation, autophagy, and immune cell regulation. It participates in pathways like the AKT/mTOR signaling pathway and is associated with the regulation of cyclin D1, cyclin-dependent kinase expressions, and CDK inhibitors [6].

In various diseases, TOB1 shows diverse functions. In gastric cancer, it can suppress the malignant phenotype of cancer cells. High levels of cTOB1/nTOB1+CD66b+ neutrophils are linked to a better prognosis, and TOB1-transfected neutrophils can affect the apoptosis and malignant phenotype of gastric cancer cells [1]. In pancreatic cancer, TOB1 is downregulated, and its overexpression reduces the proliferation of K-Ras wild-type pancreatic cancer cells [3]. In muscle, loss of Tob1 promotes muscle regeneration through muscle stem cell expansion [4]. In IBD, TOB1 restrains intestinal mucosal inflammation by suppressing Th1/Th17 cell-mediated immune responses via the Smad4/5-ID2 pathway [5]. In FMDV infection, TOB1-knockout significantly inhibits FMDV infection both in vitro and in vivo, by positively regulating the expression of RIG-I and MDA5 and inhibiting FMDV adsorption and internalization mediated by the EGFR/ERBB2 pathway [2].

In conclusion, TOB1 is a multifunctional protein with a crucial role in tumor suppression, immune regulation, and tissue regeneration. Gene knockout models, especially in mice, have been instrumental in revealing its functions in various disease conditions such as cancer, viral infection, and inflammatory bowel disease. These studies help in understanding the underlying mechanisms and potentially developing new therapeutic strategies.