MFng, also known as Manic Fringe, is a member of the Fringe family of β1,3 -N -acetylglucosaminyltransferases. It modulates Notch signaling, which is crucial in various biological processes such as cell differentiation, development, and angiogenesis [1,2,3,4,5,6,7,8].

In osteosarcoma, high MFng expression is an independent adverse prognostic factor, promoting cell proliferation and inhibiting apoptosis in U2OS cells [1]. In triple-negative breast cancer, MFng activates Notch signaling, and its expression is regulated by the GATA3/miR205-5p axis [2]. In clear cell renal cell carcinoma, MFng is highly expressed in endothelial cells, and its knockdown hinders angiogenesis and cancer cell migration [5]. Regarding pancreas development, MFng seems dispensable as no pancreatic defects were observed in MFng-overexpressing or MFng-knockout mice [3]. In heart valve development, MFng promotes endothelial-to-mesenchymal transition (EndMT) via Notch signaling, and a heterozygous MFng mutation in patients with tetralogy of Fallot-pulmonary valve stenosis was found to disrupt EndMT [6]. In ventricular chamber development, early endocardial expression of MFng promotes Dll4-Notch1 signaling for trabeculation, while its down-regulation is required for ventricular maturation [7].

In conclusion, MFng plays diverse roles in multiple biological processes and disease conditions. Its function in modulating Notch signaling is key in development and disease. The use of gene knockout and other genetic models, like in the pancreas and heart-related studies, has been instrumental in uncovering these functions, contributing to our understanding of various diseases such as osteosarcoma, breast cancer, and renal carcinoma [1,2,3,5,6,7].