DISC1 is a candidate gene for involvement in the aetiology of major psychiatric illnesses including schizophrenia. We report here the results of DISC1 yeast two-hybrid screens using human foetal and adult brain libraries. Twenty-one proteins from a variety of subcellular locations were identified, consistent with observations that DISC1 occupies multiple subcellular compartments. The cellular roles of the proteins identified implicate DISC1 in several aspects of central nervous system development and function, including gene transcription, mitochondrial function, modulation of the actin cytoskeleton, neuronal migration, glutamate transmission, and signal transduction. Intriguingly, mutations in one of the proteins identified, WKL1, have been previously suggested to underlie the aetiology of catatonic schizophrenia. (C) 2003 Elsevier Inc. All rights reserved.