The epithelial membrane protein 1 (EMP1) plays a role in neuronal differentiation and neurite outgrowth, which are involved in the pathogenesis of major depressive disorder (MDD). We sought to determine whether the EMP1 gene is implicated in MDD. We determined the mRNA expression levels of the EMP1 gene in peripheral-blood leukocytes of patients and control subjects (n=27 each). Next, we performed case-control association analyses (MDD, n=182; controls, n=350) in the Japanese population. The level of expression of the EMP1 mRNA was significantly lower in medication-free patients compared with control subjects (P<0.001). The association analysis revealed an absence of association between the polymorphisms studied and MDD, whereas a gender-specific association was observed between male controls and male patients for marker rs7315725 (permutation P=0.039). Our results suggest that the EMP1 gene may be implicated in the pathophysiology of MDD in the Japanese population. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.