KCNJ5 encodes GIRK4 (Kir3.4), a G-protein-activated inward rectifier potassium channel that mediates acetylcholine-induced potassium currents in cardiac tissue 1. The channel allows preferential potassium influx into cells, with voltage dependence regulated by extracellular potassium concentration and blockade of outward current by internal magnesium [UniProt]. Within the heart, KCNJ5 is essential for the KACh channel complex, which modulates parasympathetic nervous system effects on cardiac physiology and repolarization 2. Germline KCNJ5 mutations cause familial hyperaldosteronism type III and are implicated in long QT syndrome, though evidence for LQTS causation remains limited 3. KCNJ5 type 2 Andersen-Tawil syndrome mutations account for approximately 15% of cases and present with periodic paralysis, repolarization abnormalities, and characteristic dysmorphisms 1. Somatic KCNJ5 mutations are the most common driver of aldosterone-producing adenomas (>90% frequency), particularly in Asian populations 4. Patients with KCNJ5-mutated adenomas show younger age of onset, predominantly female presentation, higher aldosterone and lower potassium levels, and superior hypertension cure rates following adrenalectomy 56. These patients demonstrate increased left ventricular mass and diastolic dysfunction compared to non-mutated cases, with greater post-surgical improvement in cardiac function.