Zonadhesin Background Information Zonadhesin, also known as ZAN, is a sperm-specific, transmembrane protein that binds the spermatozoa to the zona pellucida of the oocyte, thereby initiating acrosomal fusion. Expressed primarily in the testis and localized to the apical region of the sperm head, Zonadhesin is a 2,812 amino acid protein that mediates species-specific cell adhesion in the sperm head and is essential for proper fertilization. Zonadhesin contains three MAM (Meprin/A5 antigen/m receptor tyrosine phosphatase) domains and four VWF (von willebrand factor) domains which mediate sperm adhesion and covalent oligomerization, respectively. Seven isoforms of Zonadhesin exist due to alternative splicing events. Four of the seven splice variants are expressed at low levels due to the presence of a premature mRNA stop codon that results in nonsense-mediated mRNA decay.