Abstract  Ca_v1.3 channels mediate Ca²⁺ influx that triggers exocytosis of glutamate at cochlear inner hair cell (IHC) synapses. Harmonin is a PDZ‐domain‐containing protein that interacts with the C‐terminus of the Ca_v1.3 α₁ subunit (α₁1.3) and controls cell surface Ca_v1.3 levels by promoting ubiquitin‐dependent proteosomal degradation. However, PDZ‐domain‐containing proteins have diverse functions and regulate other Ca_v1.3 properties, which could collectively influence presynaptic transmitter release. Here, we report that harmonin binding to the α₁1.3 distal C‐terminus (dCT) enhances voltage‐dependent facilitation (VDF) of Ca_v1.3 currents both in transfected HEK293T cells and in mouse inner hair cells. In HEK293T cells, this effect of harmonin was greater for Ca_v1.3 channels containing the auxiliary Ca_vβ₁ than with the β₂ auxiliary subunit. Ca_v1.3 channels lacking the α₁1.3 dCT were insensitive to harmonin modulation. Moreover, the ‘deaf‐circler’dfcr mutant form of harmonin, which does not interact with the α₁1.3 dCT, did not promote VDF. In mature IHCs from mice expressing the dfcr harmonin mutant, Ca_v1.3 VDF was less than in control IHCs. This difference was not observed between control and dfcr IHCs prior to hearing onset. Membrane capacitance recordings from dfcr IHCs revealed a role for harmonin in synchronous exocytosis and in increasing the efficiency of Ca²⁺ influx for triggering exocytosis. Collectively, our results indicate a multifaceted presynaptic role of harmonin in IHCs in regulating Ca_v1.3 Ca²⁺ channels and exocytosis.