Because Na+-coupled Cl− importers and their upstream regulatory serine–threonine kinases (WNK-SPAK-OSR1) are involved in maintaining intracellular ionic homeostasis as well as regulation of cell volume [2,49], inhibiting these cotransporters is a subject of interest in ischemic stroke therapy and in other forms of acute brain injury (brain trauma, SAH) where cerebral edema is a major contributor to poor clinical outcome [2,49]. This evidence concerns the gene OSR1 and brain injury.