In multiple sclerosis (MS), inflammation-induced TRPV4 channels contribute to blood-brain barrier (BBB) dysfunction. The study shows that TRPV4 expression is increased in the endothelium of MS brain tissue around active/inactive lesions, coinciding with microglia enrichment. Microglia-derived TNFα induces TRPV4 expression in brain endothelial cells, which affects barrier function by altering claudin-5 expression and promoting inflammatory mediators. TRPV4 activity enhances T cell migration across the BBB. These findings suggest that endothelial TRPV4 plays a key role in MS pathogenesis by driving BBB dysfunction and immune cell migration. TRPV4 is involved in BBB homeostasis, with increased expression under inflammatory conditions leading to barrier impairment. Inhibiting TRPV4 reduces T cell extravasation, indicating its potential as a therapeutic target. The study highlights the importance of TRPV4 in regulating BBB integrity and inflammation in MS.In multiple sclerosis (MS), inflammation-induced TRPV4 channels contribute to blood-brain barrier (BBB) dysfunction. The study shows that TRPV4 expression is increased in the endothelium of MS brain tissue around active/inactive lesions, coinciding with microglia enrichment. Microglia-derived TNFα induces TRPV4 expression in brain endothelial cells, which affects barrier function by altering claudin-5 expression and promoting inflammatory mediators. TRPV4 activity enhances T cell migration across the BBB. These findings suggest that endothelial TRPV4 plays a key role in MS pathogenesis by driving BBB dysfunction and immune cell migration. TRPV4 is involved in BBB homeostasis, with increased expression under inflammatory conditions leading to barrier impairment. Inhibiting TRPV4 reduces T cell extravasation, indicating its potential as a therapeutic target. The study highlights the importance of TRPV4 in regulating BBB integrity and inflammation in MS.