The article discusses the role of adherens junctions (AJs) and vascular endothelial cadherin (VE-cadherin) in controlling vascular permeability. Endothelial cells regulate the passage of plasma constituents and circulating cells from blood to underlying tissues, a process that is impaired in various pathological conditions such as inflammation, sepsis, ischemia, and diabetes. AJs, composed mainly of VE-cadherin, play a crucial role in maintaining endothelial integrity. Factors like vascular endothelial growth factor (VEGF) can induce the tyrosine phosphorylation of VE-cadherin, leading to increased vascular permeability and leukocyte diapedesis. Additionally, the internalization and cleavage of VE-cadherin can disrupt AJs, further enhancing permeability. The article explores the molecular mechanisms underlying these processes, including the involvement of kinases, phosphatases, and other signaling proteins. It also discusses potential pharmacological strategies to modulate endothelial permeability, such as using inhibitors of SRC and other kinases, agents that increase cAMP levels, and inhibitors of lytic enzymes. The authors emphasize the importance of understanding the complex interplay between transcellular and paracellular pathways in controlling vascular permeability and suggest that further research is needed to fully elucidate these mechanisms.The article discusses the role of adherens junctions (AJs) and vascular endothelial cadherin (VE-cadherin) in controlling vascular permeability. Endothelial cells regulate the passage of plasma constituents and circulating cells from blood to underlying tissues, a process that is impaired in various pathological conditions such as inflammation, sepsis, ischemia, and diabetes. AJs, composed mainly of VE-cadherin, play a crucial role in maintaining endothelial integrity. Factors like vascular endothelial growth factor (VEGF) can induce the tyrosine phosphorylation of VE-cadherin, leading to increased vascular permeability and leukocyte diapedesis. Additionally, the internalization and cleavage of VE-cadherin can disrupt AJs, further enhancing permeability. The article explores the molecular mechanisms underlying these processes, including the involvement of kinases, phosphatases, and other signaling proteins. It also discusses potential pharmacological strategies to modulate endothelial permeability, such as using inhibitors of SRC and other kinases, agents that increase cAMP levels, and inhibitors of lytic enzymes. The authors emphasize the importance of understanding the complex interplay between transcellular and paracellular pathways in controlling vascular permeability and suggest that further research is needed to fully elucidate these mechanisms.