Objective: The Ca²⁺-dependent release of glutamate by the photoreceptor synapse is reduced in the presence of fenamates and is dependent on the Cl^- equilibrium potential. The molecular basis underlying this effect is unclear Methods: The localisation of TMEM16B in the retina was analyzed by immunohistochemistry. GST pull-down assays were used to investigate protein-protein interaction.TMEM16B was heterologously expressed in HEK293 cells and the membrane conductance was studied by patch-clamp techniques. Results: TMEM16B is an abundant protein of the photoreceptor synaptic membranes where it co- localizes with the adaptor proteins PSD95, VELI3 and MPP4. The C-terminus of TMEM16B specifically binds PSD95. TMEM16B related membrane conductance appeared as a Ca²⁺-dependent Cl channel with fast activation and outward rectification. The channel was rather insensitive DIDS but sensitive to fenamates. Conclusion: TMEM16B shows Ca²⁺-dependence, blocker sensitivity and rectification comparable to Ca²⁺-dependent Cl channels in the photoreceptor inner segments. With the capability to interact with synaptic proteins TMEM16B is a strong candidate for Cl channel that modulates glutamate release at the photoreceptor synapse.