Unc5b, an axon guidance regulator, is also expressed in various cell types and is involved in multiple biological processes. It is a receptor for Netrin-1 and is associated with pathways such as Wnt/β-catenin signaling. Unc5b plays a crucial role in maintaining the integrity of barriers like the blood-brain barrier (BBB) and blood-retina barrier (BRB), and is also implicated in processes such as neural differentiation, angiogenesis, and macrophage function in the context of diseases [1,3].

In in vivo studies, inducible endothelial-specific deletion of Unc5B in adult mice led to BBB leak, with changes in barrier-related gene expression and a decrease in Wnt/β-catenin signaling, indicating its role in maintaining BBB integrity [1]. Conditional deletion of Unc5b in monocytes and macrophages of mice with advanced atherosclerosis resulted in a decrease in atherosclerotic plaque burden, reduced plaque complexity, and improved macrophage efferocytotic capacity, suggesting it as a therapeutic target for atherosclerosis [2].

In conclusion, Unc5b is essential for maintaining the integrity of neurovascular barriers and has a significant impact on macrophage-related processes in atherosclerosis. The use of gene knockout and conditional knockout mouse models has revealed its critical functions in these disease-relevant biological processes, providing potential therapeutic targets for CNS diseases and atherosclerosis.