The University of South Florida (USF) received a $187,500 Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) to investigate the role of the extracellular signaling protein Reelin in Fragile X Syndrome (FXS). The goals of this 2-year research project are to: 1) validate the efficacy of a gene therapy approach using an optimized Reelin fragment to rescue cognitive deficits in an FXS mouse model, and 2) determine the mechanism by which increased Reelin signaling indirectly compensates for the loss of the FMR1 gene product, FMRP, in FXS. The proposed research seeks to advance understanding of synaptic dysregulation in FXS and explore Reelin as a potential therapeutic target, as previous work by the USF team has shown Reelin supplementation can fully restore cognitive function in FXS mice.