Tissue-nonspecific alkaline phosphatase (TNAP) is an ectoenzyme bound to the plasma membranes of numerous cells via a glycosylphosphatidylinositol (GPI) moiety. TNAP is one of many proteins localized to Brain microvascular endothelial cells (BMECs), and is highly abundant in human and rodent cerebral microvessels [33]. There are four alkaline phosphatase (AP) isoenzymes in humans and they include: TNAP, germ cell alkaline phosphatase (GCAP), intestinal alkaline phosphatase (IAP), and placental alkaline phosphatase (PLAP). Although TNAP is ubiquitous in many tissue, it is most highly expressed in bone, liver, intestine, kidney, and brain, while the three other AP isoenzymes are expressed in the tissues for which they are named. TNAP is also highly expressed in cerebral microvessels.