In mature spermatozoa, VDAC2 and VDAC3 are abundant in the outer dense fibers of flagellum, a non-membranous structure. VDAC2 is also found in the acrosomal membrane or plasma membrane of sperm head. Functionally, VDAC is implicated in spermatogenesis, sperm maturation, motility and fertilization. However, the exact localization and function of three VDAC subtypes in mammalian spermatozoa have not yet been established. Mammalian spermatozoa are a kind of highly compartmentalized cells. Proteins involved in the acrosomal status and acrosome reaction are usually located in the head or acrosomal region. The intact acrosome is a prerequisite for normal acrosome reaction and sperm-egg fusion. It is now generally agreed that acrosome reaction is a Ca2+ Benazepril dependent event. The occurrence of acrosome reaction has a Gelsenicine positive correlation with intracellular Ca2+ concentration. Acrosome reaction can therefore be induced through co-incubation of spermatozoa with calcium ionophore A23187 in vitro. VDAC2 has been discovered in the acrosomal membrane or plasma membrane of bovine sperm head. The co-incubation of bovine spermatozoa with anti-VDAC2 antibody can cause an increased loss of acrosomal integrity and noticeable changes in the morphology of sperm head, which are presumably due to the alteration of the intracellular ion concentration. VDAC in somatic cells contains Ca2+ binding site and regulates Ca2+ transmembrane transport. These data prompt us to hypothesize that VDAC2 incorporates in the sperm membrane and regulates the acrosomal integrity and acrosome reaction through mediating Ca2+ transmembrane flux, a typical feature of VDAC as a membrane channel protein. In a previous study, we have confirmed the presence of VDAC in human spermatozoa. Up to now, there is no knowledge about the respective distribution and function of three VDAC subtypes in human spermatozoa. The purpose of this study is to study the presence of VDAC2 in human spermatozoa for the first time, and to investigate its functional role in the acrosomal integrity and acrosome reaction using anti-VDAC2 monoclonal antibody. Although there are several researches about VDAC in male mammalian testis and spermatozoa, the respective presence and function of three VDAC subtypes have not yet been established. In the present study, we focused on the presence and functional role of VDAC2 in human spermatozoa.