Accumulating evidence from both genetic and clinico-pharmacological studies suggests that D-serine, an endogenous co-agonist to the NMDA subtype glutamate receptor, may be implicated in schizophrenia (SZ). Although an association of the genes for D-serine degradation, such as D-amino acid oxidase and G72, has been reported, the implication of the D-serine synthesis in SZ has been unclear. We previously reported PICK1 as a potential binding protein of the D-serine synthesizing enzyme, serine racemase (SR) (Fujii et al, SFN 2002). Here we confirm endogenous protein binding of SR and PICK1 in glial cells. The gene coding for PICK1 is located at chromosome 22q13, a region frequently linked to SZ. In a case-control association study using well-characterized Japanese subjects, we observe an association of the PICK1 gene with SZ, which is specific for disorganized SZ. Our finding implicating PICK1 as a susceptibility gene for SZ enlarge a putative role of D-serine in the disease.