HE2 is a human epididymis specific sperm binding secretory protein expressed by SPAG11 gene (chromosome 8p23-p22), a 103aa protein adopts a typical antigenic pattern with a subacrosomal equatorial distribution on the sperm head, this localization of HE2 with Beta-defensins in the epithelial defense system of epididymal duct have developed mechanism to fight ascending infections, including local production of these antimicrobial peptides and proteins. The regionalized epididymal expression of the HE2 and its isoforms suggests that they exert their effects at different times in the controlled sequence of sperm modification, maturation, binding and a direct role in fertilization. HE2 represents 3 major isoforms, HE2-alpha, HE2-beta and HE2-gamma, all variants have a common 71 residue N terminus but various C termini, these variations at C termini is due to frame shifting deletions. Thus, identical sequences and deletion, start and stop points indicate that HE2 isoforms are derived from al