Patients treated with inhibitors that target mGluR develop tolerance to these pharmacological interventions. A more detailed understanding of how mGluR signaling is altered in FXS is required to develop effective therapies for FXS. One promising therapeutic approach is to target proteins downstream of mGluR, such as the calcium-binding protein Neuronal Calcium Sensor-1 (NCS-1) and its Drosophila orthologue Frequenin (Frq). NCS-1/Frq levels are altered in FXS and a missense mutation has been associated with autism. Our broad goal is to understand the role of NCS-1/Frq in synaptic and cognitive effects found in FXS.