We examined the association of schizophrenia (SCZ) and dihydropyrimidinase-like 2 (DPYSL2), also known as collapsin response mediator protein 2, which regulates axonal growth and branching. We genotyped 20 tag single nucleotide polymorphisms (SNPs) in 1464 patients and 1310 controls. There were two potential associations in a screening population of 384 patients and 384 controls (rs2585458: P=0.046, rs4733048: P=0.014). However, we could not replicate these associations in a confirmatory population of 1080 patients and 926 controls (rs2585458: P=0.39, rs4733048: P=0.70) or a joint analysis (rs2585458: P=0.72, rs4733048: P=0.10). We conclude that DPYSL2 does not have a major function in SCZ in Japanese subjects.