KCNF1 (Kv5.1) is a regulatory alpha-subunit of voltage-gated potassium channels that modulates Kv2 channel function through heteromeric assembly with KCNB1 or KCNB2 1. When coassembled, KCNF1 modulates channel expression and gating kinetics, accelerating inactivation while markedly slowing it when coexpressed with Kv2 subunits, with effects dependent on subunit stoichiometry. KCNF1 alone cannot produce functional potassium currents [UniProt]. In neurons, Kv2/KCNF1 heteromeric channels show distinct pharmacological profiles and contribute substantially to dorsal root ganglion conductances 1. Beyond ion channel regulation, KCNF1 functions ion-independently as a nuclear protein in lung cancer pathogenesis, promoting NSCLC through ITGB4 signaling; silencing KCNF1 reduces proliferation and enhances cisplatin sensitivity 2. Clinically, KCNF1 autoantibodies have been identified in treatment-resistant epilepsy patients with early seizure onset, including Lennox-Gastaut and mesial temporal lobe epilepsy cases, suggesting potential autoimmune pathophysiology 3. KCNF1 is also implicated in renal ciliogenesis 4, cancer prognosis [PMID:36397112; 57], and alcohol preference 6. These findings indicate KCNF1 has dual roles in ion channel modulation and non-canonical cancer-related signaling.