The conceptualization of reelin as a pleiotropic extracellular matrix molecule with multiple roles in brain development and in adult brain plasticity captured the attention of Erminio Costa and Alessandro Guidotti, who hypothesized that reelin expression could be dysregulated in psychotic disorders (i.e., schizophrenia), and that baseline levels of reelin could be an important vulnerability factor in a two-hit neurodevelopmental hypothesis for the development of schizophrenia. The gene discussed is RELN; the disease is schizophrenia.