The voltage-gated potassium channel Kv2.1 is abundantly expressed in many mammalian central neurons, and its hyperactivity is associated with epileptic seizures and ischemic insults. Modification of the channel by phosphorylation and dephosphorylation alters its gating, but attempts to identify candidate phosphorylation sites have been confounded by the unusually large number of predicted phosphorylation sites. Park et al. have used an unbiased mass spectrometric approach to identify multiple in vivo phosphorylation sites on Kv2.1. Mutational analysis of these sites reveals that variable phosphorylation of the channel results in graded changes in the gating of Kv2.1 ionic currents. Such a graded regulatory mechanism could play a key homeostatic and neuroprotective role.