Genetic defects in the hotspot of inwardly rectifying K+ (Kir) channels and their metabolic consequences: A review

► Inwardly rectifying potassium (Kir) channels are ubiquitous. ► Control cellular events from neurotransmitter release to epithelial transport. ► Genetic and molecular understanding of disease-related Kir channel mutations. ► Mutations positioned within a regulatory cytoplasmic “hotspot”. ► Metabolic regulation pathways provide insight into phenotypic heterogeneity.