Bves, also known as Blood Vessel Epicardial Substance (BVES), is a transmembrane protein and a member of the Popeye domain-containing gene family [1,3]. It is evolutionarily conserved and postulated to play roles in cell adhesion, cell motility, and junctional signaling [1,3]. Emerging evidence indicates its importance in maintaining epithelial integrity and muscle homeostasis, and it is involved in pathways such as cAMP, WNT, and degradation of the oncogene c-Myc [2].

In mouse models, BVES deletion reduces muscle mass, impairs muscle performance, and causes worse intestinal injury and inflammation [2,4]. Mice lacking BVES also show promotion of tumor formation, indicating its role in suppressing tumorigenesis [2]. In LGMDR25 mouse models, systemic AAV9-BVES delivery ameliorates muscular dystrophy, improving muscle-related phenotypes and cardiac function [5]. In VSMC-specific Bves-overexpressing rat aortic grafts, neointimal lesion formation is attenuated, suggesting its role in maintaining VSMC contractile phenotype and protecting against transplant vasculopathy [6]. In zebrafish, bves knockdown leads to ventricular outflow tract stenosis and defects in heart development, and BVES downregulation may be associated with RVOT stenosis in non-syndromic tetralogy of fallot [7].

In conclusion, Bves is crucial for maintaining muscle and epithelial integrity, and its functions are revealed through various gene-knockout models in different disease areas. These models demonstrate its significance in muscle-related diseases like muscular dystrophy, in intestinal inflammation and cancer, as well as in heart-related diseases such as tetralogy of fallot. The study of Bves in these models helps to understand its biological functions and provides potential therapeutic targets for related diseases.