KCNN2 encodes the small-conductance calcium-activated potassium channel 2 (SK2), a voltage-independent potassium channel that mediates calcium-dependent potassium ion transmembrane transport 1. The channel constitutively binds calmodulin, which upon calcium binding triggers a conformational change enabling channel opening with a characteristic single-channel conductance of ~3 picosiemens 12. SK2 displays inward rectification that reduces outward potassium conductance at positive membrane potentials, controlled by positively charged residues in the S6 transmembrane domain 1. Structurally, extracellular S3-S4 loops form a β-hairpin canopy with an aromatic center over the pore, with inter-subunit hydrogen bonds tethering the selectivity filter 3. SK2 plays critical roles in cardiac and neuronal physiology. It mediates repolarization during atrial cardiac action potentials 4, and KCNN2 genetic variants associate with ventricular tachyarrhythmias and sudden cardiac death risk 5. N2O-induced SK2 channel inhibition activates layer 5 prefrontal neurons, contributing to antidepressant effects 6. Clinically, heterozygous KCNN2 variants cause autosomal-dominant neurodevelopmental movement disorders including developmental delay, cerebellar ataxia, and extrapyramidal symptoms, likely through haploinsufficiency 27. Large-scale exome sequencing identified KCNN2 variants in dystonia patients, supporting its role in movement disorder pathogenesis 8. Additionally, SK2 regulates migration and chemosensitivity in ovarian cancer cells 9.