Olfactory Deficits in Fragile X Syndrome

ABSTRACT Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and a major genetic cause of autism spectrum disorders (ASDs). It results from the loss of fragile X mental retardation protein (FMRP), an mRNA‐binding protein critical for synaptic development and plasticity. Although sensory processing abnormalities are well recognized in FXS, the olfactory system remains relatively underexplored in both human and animal studies. Evidence from rodent and drosophila models reveals that FMRP loss profoundly alters olfactory circuitry and function. In Fmr1 knockout mice, aberrant mitral cell dendritic morphology and increased granule cell spine density disrupt excitation/inhibition (E/I) balance, leading to circuit hyperexcitability and impaired odor discrimination. Similarly, dfmr1 ‐deficient flies show reduced GABAergic inhibition, broadened odor tuning, and altered odor‐guided behaviors, reflecting conserved mechanisms of synaptic dysregulation. These findings parallel disruptions seen in other sensory systems, underscoring the olfactor