The authors identified a conserved family of genes related to the Drosophila eag gene, which encodes a distinct type of voltage-activated potassium (K⁺) channel. Three related genes were isolated from Drosophila, mouse, and human tissues. One gene is the mouse counterpart of eag, while the other two represent additional subfamilies. The human gene maps to chromosome 7. Members of this family share at least 47% amino acid identity in their hydrophobic cores and all contain a segment homologous to a cyclic nucleotide-binding domain (cNBD). Sequence comparisons indicate that these genes are most closely related to vertebrate cyclic nucleotide-cycled cation channels and plant inward-rectifying K⁺ channels. The discovery of this family extends the known diversity of K⁺ channels and has important implications for understanding the structure, function, and evolution of voltage-sensitive ion channels. The authors used low-stringency screens and degenerate PCR to isolate relatives of eag from Drosophila, mouse, and human tissues, and their findings suggest that the eag family contains at least three subfamilies, similar to the Sh family of voltage-activated K⁺ channels. The conservation of eag polypeptide sequences from Drosophila to mammals indicates that these channels may play a crucial role in maintaining normal neuronal excitability. The presence of a cNBD in the eag family suggests that it may be an evolutionary link between voltage-activated K⁺ channels and cyclic nucleotide-gated cation channels.The authors identified a conserved family of genes related to the Drosophila eag gene, which encodes a distinct type of voltage-activated potassium (K⁺) channel. Three related genes were isolated from Drosophila, mouse, and human tissues. One gene is the mouse counterpart of eag, while the other two represent additional subfamilies. The human gene maps to chromosome 7. Members of this family share at least 47% amino acid identity in their hydrophobic cores and all contain a segment homologous to a cyclic nucleotide-binding domain (cNBD). Sequence comparisons indicate that these genes are most closely related to vertebrate cyclic nucleotide-cycled cation channels and plant inward-rectifying K⁺ channels. The discovery of this family extends the known diversity of K⁺ channels and has important implications for understanding the structure, function, and evolution of voltage-sensitive ion channels. The authors used low-stringency screens and degenerate PCR to isolate relatives of eag from Drosophila, mouse, and human tissues, and their findings suggest that the eag family contains at least three subfamilies, similar to the Sh family of voltage-activated K⁺ channels. The conservation of eag polypeptide sequences from Drosophila to mammals indicates that these channels may play a crucial role in maintaining normal neuronal excitability. The presence of a cNBD in the eag family suggests that it may be an evolutionary link between voltage-activated K⁺ channels and cyclic nucleotide-gated cation channels.