Schizophrenia (SCZ) is a multifactorial chronic and disabling mental disease. The specific genetic variants contributing to disease complex phenotype are largely unknown. Growing amount of evidence suggested that aberrant synaptic connectivity contributes to SCZ pathogenesis. From this point of view, complexin-2, a presynaptic regulatory protein, represents here a special interest, since it has been recently shown that genetic variants of the CPLX2 gene may affect current cognitive performance in patients with SCZ. A specific objective of this study was to evaluate if tagging single nucleotide polymorphisms (rs3892909, rs1366116) of gene encoding complexin-2 protein (CPLX2) linked to SCZ and to examine their relationships with complexin-2 blood levels. DNA samples of 260 patients with SCZ and 260 sex- and age-matched healthy controls were genotyped for the selected polymorphisms by application of polymerase chain reaction with sequence-specific primers, and concentration of complexin-2 in the blood plasma was determined using the enzymelinked immunosorbent assay. All study subjects were unrelated Armenians. According to the obtained results, in the patients group both the frequency distribution and carriage rate of the CPLX2 rs1366116*T minor allele were higher than in controls. On the contrary, the frequency distribution and carriage rate of the CPLX2 rs3892909*T minor allele in control group were higher than in patients. This data suggested that the presence of the CPLX2 rs1366116*T allele increases susceptibility to SCZ, whereas the rs3892909*T allele of the CPLX2 decreases the risk of SCZ. Furthermore, we found that CPLX2 rs1366116*T heterozygosity is associated with earlier disease onset. No difference between complexin-2 plasma levels in patients and controls and no significant interaction between complexin-2 plasma levels and CPLX2 genotypes in both groups were observed. In summary, we concluded that the CPLX2 rs1366116*T variant represents a risk factor of SCZ, and that, at the same time, the CPLX2 rs3892909*T variant is protective against SCZ.