KCNH6 encodes a pore-forming subunit of voltage-gated inwardly rectifying potassium channels characterized by distinctive gating kinetics: rapid inactivation during depolarization with slow deactivation during repolarization, resulting in large inward currents 1. Primary functions include potassium ion transmembrane transport and regulation of cardiac and pancreatic cell membrane potential 12. Mechanistically, KCNH6 regulates pancreatic β-cell insulin secretion by controlling membrane depolarization and intracellular calcium homeostasis 13. The channel protects β-cells from endoplasmic reticulum (ER) stress-induced apoptosis; KCNH6 knockout increases ER stress, intracellular calcium, and β-cell apoptosis, while overexpression attenuates ER stress responses 2. Additionally, m6A RNA modification regulates KCNH6 expression in a YTHDF1-dependent manner, controlling fibroblast-to-myofibroblast transition in pulmonary fibrosis 4. Disease relevance includes: KCNH6 mutations causing hypoinsulinemia and hyperglycemia in humans and mice 32; involvement in pulmonary fibrosis pathogenesis 4; and potential role as a glioblastoma prognostic biomarker 5. Clinical significance: Berberine and cisapride inhibit KCNH6 currents to stimulate glucose-dependent insulin secretion, with berberine demonstrating efficacy in human clinical trials without causing hypoglycemia 13. KCNH6-targeting represents a promising therapeutic strategy for diabetes treatment.