KCNA2 encodes Kv1.2, a voltage-gated potassium channel highly expressed in the central nervous system that plays critical roles in neuronal excitability and synaptic function 1. The channel forms tetrameric complexes that regulate potassium ion transport across neuronal membranes, preventing aberrant action potential firing and maintaining proper neuronal output 2. KCNA2 mutations cause developmental and epileptic encephalopathy (DEE), with distinct genotype-phenotype correlations based on functional effects 1. Loss-of-function mutations typically present with focal seizures, Rolandic epileptic discharges that may progress to electrical status epilepticus during sleep (ESES), and developmental regression after seizure onset 3. Gain-of-function mutations are associated with more severe phenotypes including neonatal-onset seizures, generalized epileptic activity, severe developmental delay, and brain atrophy 1. Mixed gain-and-loss-of-function variants cause the most severe early-onset phenotypes with both generalized and focal seizures 1. Beyond epilepsy, KCNA2 variants are associated with intellectual disability, autism spectrum disorder, and movement disorders 2. Additionally, KCNA2 autoantibodies have been identified in neuropsychiatric conditions, with some patients responding to immunotherapy 4. Recent research also suggests KCNA2's involvement in cancer cell proliferation through Hippo/YAP signaling pathways 5.