Sprouty was discovered and initially described by Hacohen et al. in 1998 as an inhibitor of fibroblast growth factor (FGF)-mediated tracheal branching (hence its name) in Drosophila melanogaster (Hacohen et al. 1998). Later, they further defined it as a common antagonist of FGF and epidermal growth factor (EGF) signaling pathways (Kramer et al. 1999). Along with the discovery of the Drosophila gene, or dSpry, they performed a search of the expressed sequence tag (EST) database and identified three human homologs of dSpry which were designated hSpry1, hSpry2, and hSpry3 (Hacohen et al. 1998). The fourth mammalian homolog (Spry4) was discovered later in mice (de Maximy et al. 1999) and humans (Leeksma et al. 2002). Since then, an expanding body of evidence has continued to support the crucial role of Sprouty in the regulation of key cellular processes and biological events, mainly as a modulator of receptor tyrosine kinase (RTK) signaling...