The mammalian zona pellucida is composed of three major glycoproteins, ZP1, ZP2 and ZP3. ZP2 has been implicated as a secondary sperm receptor that binds sperm only after the induction of the sperm acrosome reaction. Both ZP2 and ZP3 are modified by the zona reaction; ZP2 undergoes a proteolytic cleavage and ZP3 loses its ability to induce the acrosome reaction and its sperm receptor activity. During the process of fertilization, the initial interaction between male and female gametes is mediated by a sperm receptor, ZP3, which resides in the extracellular glycoprotein matrix (zona pellucida) surrounding the oocyte. The sperm receptor function of the ZP3 molecule plays a key role in the first step of the fertilization process. Following sperm-oocyte binding, ZP3 triggers the sperm acrosome reaction that releases the protein machinery, enabling a spermatozoon to penetrate the zona pellucida.