Low-voltage-activated (LVA) Ca²⁺ channels are widely distributed throughout the CNS and are important determinants of neuronal excitability, initiating dendritic and somatic Ca²⁺ spikes that trigger and shape the pattern of action potential firing. Here, we define a molecular mechanism underlying the dynamic regulation of α_1H channels (Ca_v3.2), by Ca²⁺/CaM-dependent protein kinase II (CaMKII). We show that channel regulation is selective for the LVA α_1H Ca²⁺ channel subtype, depends on determinants in the α_1H II-III intracellular loop, and requires the phosphorylation of a serine residue absent from unregulated α_1G (Ca_v3.1) channels. These studies identify the α_1H channel as a new substrate for CaMKII and provide the first molecular mechanism for the direct regulation of T-type Ca²⁺ channels by a protein kinase. Our data suggest a novel mechanism for modulating the integrative properties of neurons.