Hearing relies on Ca2+influx-triggered exocytosis in cochlear inner hair cells (IHCs). Here we studied the role of the Ca2+channel subunit CaVβ2in hearing. Of the CaVβ1–4mRNAs, IHCs predominantly contained CaVβ2. Hearing was severely impaired in mice lacking CaVβ2in extracardiac tissues (CaVβ2−/−). This involved deficits in cochlear amplification and sound encoding. Otoacoustic emissions were reduced or absent inCaVβ2−/−mice, which showed strongly elevated auditory thresholds in single neuron recordings and auditory brainstem response measurements.CaVβ2−/−IHCs showed greatly reduced exocytosis (by 68%). This was mostly attributable to a decreased number of membrane-standing CaV1.3 channels. Confocal Ca2+imaging revealed presynaptic Ca2+microdomains albeit with much lower amplitudes, indicating synaptic clustering of fewer CaV1.3 channels. The coupling of the remaining Ca2+influx to IHC exocytosis appeared unaffected. Extracellular recordings of sound-evoked spiking in the cochlear nucleus and auditory nerve revealed reduced spike rates in theCaVβ2−/−mice. Still, sizable onset and adapted spike rates were found during suprathreshold stimulation inCaVβ2−/−mice. This indicated that residual synaptic sound encoding occurred, although the number of presynaptic CaV1.3 channels and exocytosis were reduced to one-third. The normal developmental upregulation, clustering, and gating of large-conductance Ca2+activated potassium channels in IHCs were impaired in the absence of CaVβ2. Moreover, we found the developmental efferent innervation to persist in CaVβ2-deficient IHCs. In summary, CaVβ2has an essential role in regulating the abundance and properties of CaV1.3 channels in IHCs and, thereby, is critical for IHC development and synaptic encoding of sound.