The voltage-activated L-type calcium channels Cav1.2 and Cav1.3 mediate Ca 2+ influx into neurons at the soma or at dendrites, whereas they are not observed at the presynapse. Surprisingly, in the inner ear, Cav1.3 is indispensable for signal transmission from the presynaptic cochlear inner hair cells to the postsynaptic auditory nerve fibers. Due to Cav1.3 channel clustering at ribbons, i.e., specific presynaptic structures of the hair cells, they promote Ca 2+ influx, which triggers calcium-dependent fusion of synaptic vesicles with the plasma membrane. Mutations in Cacna1d, a gene that encodes Cav1.3, result in deafness because release of the neurotransmitter glutamate at the synapses is abolished. Moreover, studies of the auditory pathway have revealed that Cav1.3 plays an important part in the central auditory system as well. Absence of the channel results in severe changes in auditory pathway cytoarchitecture and in abnormal electrophysiological performance of auditory neurons. Furthermore, developmental refinement of tonotopic inhibitory projections in sound localization circuits is disrupted. These aberrations are associated with abnormal sound processing in the auditory pathway. This goes to show that the Cav1.3 channel is essential for inner ear functioning as well as auditory pathway development and performance. Cacna1d therefore represents a prototypal deafness-associated gene, in which mutations result in both peripheral and central auditory deficiencies. This, in turn, has implications for auditory rehabilitation using cochlear implants that address only peripheral dysfunctions. Exploratory research into the closely related Cav1.2 isoform points to an important role of this channel in acoustic trauma. Cav1.2 is mainly expressed in the auditory nerve, but apparently not essential for normal auditory function. Loss of function of the channel, however, does influence the effects of traumatic noise exposure. Loss of this channel induced by noise trauma results in reduced auditory threshold increase-as compared with the control group. This phenomenon points to the fact that Cav1.2-mediated Ca 2+ influx is involved in noise trauma-induced damage. Deeper insight into this function might result in new therapeutic approaches.