Channelopathies: Decoding disease pathogenesis

The deconvolution of corrupted biological pathways in disease and the translation of patient-specific molecular mechanisms into tailored management algorithms have begun to extend the reach of individualized medicine from principles to practice. A case in point is the emergent deciphering of the pathobiology underlying life-threatening human diseases caused by dysfunction in adenosine triphosphate (ATP)-sensitive potassium (K_ATP) channels. In a recent paper in Science, researchers used humanized mouse models to recapitulate a pathogenic K_ATP channel mutation and pinpoint tissue-restricted lesions that stratify the consequences of genetic variation on disease traits. Advances in the molecular medicine of K_ATP channelopathies offer new perspectives for personalized diagnosis and therapy.