Leukocyte migration across the blood-brain barrier (BBB) is a key step in the progression of brain dysfunction in systemic inflammation. The key regulatory molecules at the BBB involved in leucocyte-endothelial interaction would be promising druggable targets. Sato et al. have established the LC-MS/MS-based comprehensive absolute protein quantification system for the cluster of differentiation (CD) antigens and identified the key molecules at mouse BBB in lipopolysaccharide (LPS)-induced systemic inflammation based on their absolute protein expressions. Their findings should be helpful in the development of BBB-targeting drugs to block leukocyte migration associated with central nervous system disorders.