Tgfbr3, also known as betaglycan, is a co-receptor in the TGF-β signaling pathway. The TGF-β superfamily signaling pathways are involved in embryonic development, maintaining cellular homeostasis, and regulating immune function [1,2,3,4,5,6,7,9]. Tgfbr3 can regulate the actions of diverse TGF-β ligands [8].

In various cancers, Tgfbr3 often acts as a tumor suppressor gene. In lung cancer, its expression decreases, and the invasion, metastasis, angiogenesis, and apoptosis of lung cancer cells are closely related to its expression [1]. In breast cancer, loss of Tgfbr3 is progressive, and it supports anoikis through suppressing ATF4 signaling [2]. In papillary thyroid cancer, Tgfbr3 inhibits tumor progression by inhibiting the PI3K/AKT pathway and EMT [3]. However, in oesophageal squamous cell carcinoma, TGFBR3 is upregulated and is an independent unfavourable prognostic marker [4]. In addition, in thyroid-eye disease, the miR-103a-3p/TGFBR3 axis regulates TGF-β-induced orbital fibroblast activation and fibrosis [5]. In eosinophilic nasal polyps, MEX3B inhibits collagen production by downregulating epithelial cell Tgfbr3 mRNA stability [6]. In cardiomyocytes, the let-7-Tgfbr3-p38 MAPK signalling plays an important role in apoptosis after infarction [9].

In conclusion, Tgfbr3 is a crucial co-receptor in the TGF-β signaling pathway, significantly influencing various biological processes and disease conditions, especially in multiple types of cancers. Although there is no mention of KO/CKO mouse models in these references, the studies on Tgfbr3 in different diseases help to understand its biological functions and potential as a therapeutic target.