Neuronal and cardiac voltage-gated ion channels contain auxiliary subunits that can profoundly affect the gating of the pore-forming and voltage-sensing alpha subunits. Recent studies on the structurally similar cytoplasmic beta subunits of Ca2+ and K+ channels reveal that these subunits can also exert profound effects on the expression of the integral membrane protein channel components. The mechanisms by which these effects occur are now being elucidated through a combined approach that employs biophysical, pharmacological, cell biological and biochemical techniques.