Potassium (K + ) channels are asymmetric homotetrameric transmembrane proteins that control K + -flows across biological cell membranes . In humans, Kirs (K + inwardly rectifying) belong to a family of ~ 400 ion channel genes whose genetic mutations are often implicated in diverse cardiovascular, skeletal muscle or synaptic neuronal functions or channelopathies. Distinct mutations on the Kir-coding genes can affect the electrical excitability 3 of nerve or muscle cells, channel gating, conductance, ion selectivity, and/or signal transduction. Kir channel dysfunctions can lead to i) periodic paralysis and cardiac arrhythmias when targeting the KCNJ2 gene (KChaNnel, subfamily J, member 2) as in the Andersen-Tawil Syndrome, ii) alterations of heart electrical activity, causing arrhythmias and sudden cardiac death when targeting KCNQ1, as in the Long QT Syndrome, iii) episodes of lack of coordination when targeting KCNA1 as in Episodic Ataxia 4 , iv) ventricular arrhythmias causing sudden cardiac death, when targeting KCNH2, as in the short QT Syndrome, and other channelopathies as well as some new that may be discovered in future research.