KRIT1, also known as Krev interaction trapped 1, is a 75 kDa scaffolding protein. It plays a critical role in vascular morphogenesis and homeostasis by regulating endothelial cell phenotype, maintaining a quiescent and stable endothelial barrier, and contributing to the stability of adherens junctions and inhibiting actin stress fiber formation. It is involved in the complex machinery governing cellular redox homeostasis and responses to oxidative stress and inflammation [1,2].

Loss-of-function mutations in KRIT1 lead to the development of cerebral cavernous malformations (CCM), a cerebrovascular disease. In a mouse model with neutrophil-specific deletion of KRIT1, neutrophils had reduced ability to attach and spread on fibronectin, increased migration on it, but unchanged adhesion and migration on ICAM-1. Also, integrin activation was reduced, and neutrophil migration in response to lung inflammation was decreased [3]. Silencing KRIT1 in human aortic, coronary artery, and umbilical vein endothelial cells increased expression of proinflammatory adhesion molecules and susceptibility to apoptosis. In heterozygous KRIT1+/- mice fed a high-fructose diet, there was increased VCAM-1 expression and fat accumulation in atherosclerosis-prone regions [4].

In conclusion, KRIT1 is essential for maintaining vascular integrity, especially the endothelial barrier. Its deficiency can lead to CCM and may also be implicated in aortic endothelial dysfunction and related atherosclerotic lesions. The study of KRIT1-deficient mouse models has provided valuable insights into its role in these disease conditions, highlighting its importance in understanding the pathogenesis of certain cerebrovascular and vascular-related diseases.