While there are several approaches proposed to the isolation of the genes underlying the common complex polygenic diseases, it is clear that all have significant limitations. It is also clear that disease gene isolation will not directly lead to novel drug discovery: function must first be assigned, a proven daunting task. In the "target-rich" environment created by the genome project, where one could not possibly pursue even a small target subset, there is an advantage to carrying out a focused search of gene family members, pursuing candidate diseases. The larger the family, the more diverse its functional annotation, and the more proven its disease-causing potential, the greater the efficiency. Family members share signature features facilitating identification, and share common functional assays, facilitating the design and execution of high-throughput screening for drug lead identification. Ion channel genes form a particularly promising target set, particularly for the constellation of polygenic neuropsychiatric diseases.