KCNH2 encodes the Kv11.1 potassium channel that conducts the rapid delayed rectifier K+ current (IKr), which is essential for cardiac action potential repolarization 1. Mutations in KCNH2 cause two distinct arrhythmia syndromes: loss-of-function mutations lead to Long QT syndrome type 2 (LQT2), one of the most common forms of long QT syndrome, while gain-of-function mutations cause Short QT syndrome type 1 (SQT1) 12. Most LQT2-associated mutations disrupt channel folding, assembly, or trafficking to the cell surface, reducing functional channel expression 1. In clinical genetic testing, KCNH2 mutations account for approximately 39% of genotype-positive LQTS cases 3. The channel's location is critical for pathogenicity assessment, with mutations in transmembrane, linker, and pore regions having high predictive values for disease causation 4. Beyond cardiac function, KCNH2 has recently been identified as regulating incretin hormone secretion in intestinal enteroendocrine cells, suggesting potential therapeutic applications in diabetes and obesity 5. Novel gene therapy approaches using suppression-and-replacement strategies show promise for treating both LQT2 and SQT1 by normalizing action potential duration 6.