The beta-subunits of the KChIP family modulate properties and expression level of Kv4 channels. We report the cloning of the first splice variant of KChIP1 (KChIP1b) which contains an extra exon, rich in aromatic residues, in the amino terminus. Both splice variants interacted equally well with Kv4.2 subunits based on confocal imaging and upregulation of current density (more than five-fold). No effects on the voltage dependence of activation or inactivation were noted. However, the effects on the kinetics of recovery from inactivation were opposite: KChIP1b induced a slow component in the recovery (tau approximately 1.2 s), in contrast to the increased recovery rate (tau = 125 ms) with KChIP1a. Accordingly, frequency-dependent accumulation of inactivation was enhanced by KChIP1b but reduced by KChIP1a. Since Kv4.2 channels are involved in protection against back propagating action potentials in dendritic spines, a differential expression of either splice variant could shape the dendritic function.