Cav1.4 channels are unique among the high voltage-activated (HVA) Ca2+ channel family because they completely lack Ca2+-dependent inactivation (CDI) and display very slow voltage-dependent inactivation (VDI). Both properties are of crucial importance in ribbon synapses of retinal photoreceptors and bipolar cells where sustained Ca2+ influx through Cav1.4 channels is required to couple slow graded changes of the membrane potential with tonic glutamate release. Loss of Cav1.4 function causes severe impairment of retinal circuitry function and has been linked to night blindness in men and mice. Recently, an inhibitory domain (ICDI: inhibitor of CDI) in the C-terminal tail of Cav1.4 has been discovered that eliminates CDI by binding to upstream regulatory motifs within the proximal C-terminus. The mechanism underlying the action of ICDI is unclear. It was proposed that ICDI competitively displaces the Ca2+ sensor calmodulin (CaM). Alternatively, the ICDI domain and CaM may bind to different portions of the C-terminus and act independently of each other. In the present study, we use FRET experiments with genetically engineered CFP variants to address this issue. Our data indicate that CaM is preassociated with the C-terminus of Cav1.4 but may be tethered in a different steric orientation as compared to other Ca2+ channels. We also find that CaM is important for Cav1.4 function because it increases current density and slows down voltage-dependent inactivation. Our data show that the ICDI domain selectively abolishes CDI while it does not interfere with other CaM effects.