The ADAM (A Disintegrin And Metalloprotease) family comprises membrane-spanning multi-domain proteins containing a metalloproteinase-like domain and a disintegrin-like domain. Approximately half of the ADAMs are catalytically active metalloproteases that shed a broad range of substrates, such as cytokines, growth factors, receptors, adhesion molecules [1,2]. Recent gene-disruption studies in mice have disclosed a physiological role of each ADAM. For example, ADAM10, ADAM17 and ADAM19 are critical for normal development by providing growth signals at the correct times and places [3-6]. In contrast, the functions of ADAM8, ADAM9, ADAM12 and ADAM15 are not essential for embryogenesis, suggesting a possible functional redundancy with other protease [7-10]. The remaining half, which are non-protease-ADAMs, are thought to be adhesion molecules. More than ten ADAMs have been shown to support integrin-mediated cell adhesion in vitro [11]. More recently, the finding has been reported that integrin-mediated cell migration of tissue culture cells can be controlled by distinct ADAMs [12]. In C. elegans, unc-71 gene coding a non-protease-ADAM protein have been shown to be involved in cell migration events in vivo [13]. However, the physiological roles of mammalian non-protease-ADAMs are poorly understood in vivo. Genetic deletion studies in mice have shown that both Adam2-null and Adam3-null male mutants are infertile and their spermatozoa lack egg-binding abilities [14-16]. The precise mechanism is under investigation [17].