CaBP1-8 are neuronal Ca 2+ -binding proteins with similarity to calmodulin (CaM). Here we show that CaBP4 is specifically expressed in photoreceptors, where it is localized to synaptic terminals. The outer plexiform layer, which contains the photoreceptor synapses with secondary neurons, was thinner in the Cabp4 −/− mice than in control mice. Cabp4 −/− retinas also had ectopic synapses originating from rod bipolar and horizontal cells that extended into the outer nuclear layer. Responses of Cabp4 −/− rod bipolars were reduced in sensitivity about 100-fold. Electroretinograms (ERGs) indicated a reduction in cone and rod synaptic function. The phenotype of Cabp4 −/− mice shares similarities with that of incomplete congenital stationary night blindness (CSNB2) patients. CaBP4 directly associated with the C-terminal domain of the Ca v 1.4 α 1 -subunit and shifted the activation of Ca v 1.4 to hyperpolarized voltages in transfected cells. These observations indicate that CaBP4 is important for normal synaptic function, probably through regulation of Ca 2+ influx and neurotransmitter release in photoreceptor synaptic terminals.L-type Ca 2+ channels are involved in neuronal differentiation and outgrowth and in synaptic plasticity 1,2 . At many ribbon synapses, Ca 2+ influx through L-type Ca 2+ channels triggers neurotransmitter release 3-5 . The α 1 -subunit of the L-type Ca v 1.4 channel (Ca v 1.4α1) is specific to photoreceptors and is present at highest density in the synaptic terminals 5,6 . Compared with other L-type Ca 2+ channels, Ca v 1.4 channels are activated at relatively more negative voltages and show slow inactivation 7-9 , important properties for the ability of photoreceptors to sustain continual glutamate release in the dark 4,10 . Null mutations in Ca v 1.4α1 are responsible for an X-linked disorder, CSNB2 (refs. 11 ,12 ). ERGs of these patients indicate that a deficit may occur in transmission of signals from rod photoreceptors to bipolar cells. In mice, deletion of the β 2 -subunit, another component of the photoreceptor L-type channel, alters the expression of Ca v 1.4 and produces a phenotype similar to that seen in CSNB2 patients 13 .CaBPs, a subfamily of calmodulin (CaM)-like neuronal Ca 2+ -binding proteins 14 , modulate voltage-dependent Ca 2+ channels (VDCCs) and inositol triphosphate receptors 15-17 . Here we show that CaBP4, which has only been partially characterized in silico 14 , is found specifically