The Kell blood group is constituted by two covalently linked antigens at the surface of red blood cells, Kell and Kx. Whereas Kell is a metalloprotease with demonstrated in vitro enzymatic activity, the role of Kx thereon, and/or alone, remains unknown, although its absence is linked to the McLeod syndrome, a neuroacanthocytosis. In the central nervous system, the expression of Kell and XK has been suggested, but their expression patterns remain uncharacterized, as are the post-translational pathogenic mechanisms involved in the development of the McLeod syndrome. The distributions of Kell and XK were thus studied by in situ hybridization as well as immunohistochemistry in rodent and human brain. The results reveal an independent localization of the two constituents of the Kell blood group, XK (Kx) being expressed throughout this tissue, whereas Kell expression is restricted to red blood cells in cerebral vessels. The XK protein is shown to be neuronal, located mainly in intracellular compartments, suggesting a cell specific trafficking pattern, possibly associated with specific physiological functions.