Recently, the AD genetic risk factor PICALM, which encodes the phosphatidylinositol-binding clathrin assembly (PICALM) protein involved in the endocytosis of various cell surface receptors, was reported to influence Aβ clearance across the BBB through regulating the function of LRP1 in brain endothelial cells (28). The gene discussed is PICALM; the disease is Alzheimer disease.