KCNA5 encodes Kv1.5, a voltage-gated potassium channel that mediates the atrial-specific ultra-rapid delayed rectifier potassium current (IKur), critical for atrial action potential repolarization 1. The channel exhibits faster depolarization kinetics and distinctive inactivation properties. KCNA5 functions through protein-protein interactions; FHL1 scaffolding protein associates with KCNA5 to enhance current density and modulate voltage-dependent activation 1. SNAP25-dependent membrane trafficking regulates Kv1.5 surface expression and internalization; SNAP25 downregulation increases membrane Kv1.5 levels, shortening atrial refractory period and increasing atrial fibrillation susceptibility 2. Pathologically, KCNA5 dysfunction associates with atrial fibrillation (AF), with reduced channel expression detected in AF patient atria; KCNA5 interacts with connexin proteins involved in atrial electrical remodeling 3. Loss-of-function variants (Arg184Pro, Gly384Arg) identified in pulmonary arterial hypertension (PAH) patients impair channel activity and reduce apoptosis in pulmonary artery smooth muscle cells, affecting vascular homeostasis 4. Conversely, KCNA5 overexpression enhances K+ efflux and apoptosis in vascular cells, suggesting therapeutic potential for PAH 5. KCNA5 polymorphisms show limited association with PAH susceptibility in meta-analysis 6. Recent evidence identifies KCNA5 as a drug target affecting brain functional activity 7.