Membrane fusion initiates many important events including fertilization, muscle development, synaptic transmission, and enveloped virus infections. My laboratory has probed the mechanisms of proteins that mediate fusion, and hence infection, by enveloped viruses including influenza virus and retroviruses. A working hypothesis has been that similar proteins may be used during cell-cell fusion events such as sperm-egg fusion. Based on an interest in sperm-egg fusion, my laboratory cloned and sequenced fertilin alpha and beta in 1992 (Blobel et al. 1992. Nature. 356:248 252). Fertilin alpha and beta are sperm surface proteins that are critically involved in fertilization. They are also the founding members of the ADAM (a disintegrin and metalloprotease) family of proteins (see the White Lab website for more information on ADAMs). As outgrowths of these findings we have been exploring the interaction of ADAM disintegrin domains with eggs. In the process we provided the first evidence that the integrin-associated tetraspan protein, CD9, plays a pivotal role in the process of sperm-egg fusion. Consistent with our conclusion, female mice lacking CD9 show severely reduced fertility due to a block in sperm-egg fusion. We are currently exploring the role of CD9 in sperm-egg fusion.