During the last 10 years, we have witnessed major progress in the genetic study of schizophrenia, but gene-mapping efforts have been hampered by the complex mode of inheritance and the likelihood of multiple genes of small effect. In view of the complexity, it may be instructive to understand the biological bases for pathogenesis. Extensive disruption in circadian function is known to occur among schizophrenia patients. If circadian dysfunction can be established as an 'endophenotype' for schizophrenia, it may not only enable the identification of more homogenous sub-groups, but also facilitate the genetic analyses. Therefore, circadian dysfunction maybe underlies the pathogenesis of schizophrenia and would be logical to investigate polymorphisms of genes encoding key proteins that mediate circadian rhythms. Cryptochrome1 (Cry1), located in a chromosomal region 12q23-q24.1, performs predominantly regulatory function in circadian clock and which is close to a linkage hotspot (12q24) of schizophrenia. Recent studies also found that Cry1 gene interacted with antipsychotic drugs and dopamine system which played a core role in the pathophysiology of schizophrenia. Based on these findings, we speculate that Cry1 was the candidate gene of schizophrenia. The proposition may have new clues on the development of genetic study on complex diseases.