As LDL receptor family members are main receptors for Apo E (reviewed by Herz and Willnow, 1994; Hussain et al., 1999), whose E4 variant is a strong genetic risk factor for the sporadic form of Alzheimer disease (AD; (Strittmatter et al., 1993), a causal connection between disturbed Reelin signaling and neurodegeneration has been proposed ever since Apoer2 and Vldlr were first described as Reelin receptors (Cooper and Howell, 1999; Bothwell and Giniger, 2000; Herz, 2001). The gene discussed is RELN; the disease is Alzheimer disease.