Accumulating evidence has suggested that DISC1 is involved in the neurodevelopment and pathophysiology of major mental illnesses, including schizophrenia. DISC1 binds with NUDEL (Ozeki et al 2003, PNAS), and regulates microtubule dynamics and neuronal migration (Kamiya et al, SFN abstract, 2004). Here we present a detailed study on the protein interaction of DISC1 and NUDEL. We clarified that a small domain in the C-terminal DISC1 (34 amino acids coded inside exon 13) is necessary for the DISC1/NUDEL binding, by co-immunoprecipitation with various mutants of DISC1 and NUDEL. We found that two common genetic variations that led to amino acid changes in the C-terminal DISC1 resulted in altered affinity of the DISC1/NUDEL protein binding. We are now investigating whether or not these genetic variants are associated with schizophrenia.