KCNJ2 encodes Kir2.1, an inwardly rectifying potassium channel that allows potassium to flow preferentially into cells. Its voltage dependence is regulated by extracellular potassium concentration, and inward rectification is primarily mediated by internal magnesium blockade of outward current. The channel participates in establishing action potential waveform and excitability in neuronal and muscle tissues, and is essential for cardiac repolarization and skeletal muscle function. Pathogenic KCNJ2 variants cause Andersen-Tawil syndrome (ATS), an autosomal dominant channelopathy accounting for approximately 50–60% of ATS type 1 cases 1. ATS presents as a triad of periodic muscle paralysis, electrocardiographic repolarization abnormalities (QU/QUc prolongation with normal or minimally prolonged QT intervals), and characteristic dysmorphic features 1. Bidirectional ventricular tachycardia is the hallmark arrhythmia. KCNJ2 mutations also associate with familial atrial fibrillation and short QT syndrome, conditions involving gain-of-function alterations 2. Recent evidence suggests that spexin-mediated suppression of KCNJ2 transcription via GALR2/CREB signaling reduces atrial fibrillation susceptibility 3. Additionally, KCNJ2 upregulation in dermal fibroblasts promotes hair growth through membrane hyperpolarization and enhanced Wnt signaling 4. At the population level, gnomAD v4.1 classifies this gene as loss-of-function tolerant (LOEUF=0.65); this is distinct from clinical pathogenicity in disease contexts where 66 pathogenic variants are documented in ClinVar. Dronedarone targets this channel for atrial fibrillation management.