This talk will focus on the critical role played by claudin-5 at the blood-brain barrier (BBB). Claudin-5 is the most enriched tight junction component at the BBB and its dysregulation has been implicated in a range of neurological and neuropsychiatric disorders. Here, the focus will be on understanding how and why claudin-5 becomes disrupted at the BBB. The talk will bring in both pre-clinical and clinical research based approaches to understanding regulation of the BBB in health and disease.