The fragile X mental retardation protein (FMRP) plays a role in the control of local protein synthesis in the dendrites. Loss of its production in fragile X syndrome is associated with transcriptional dysregulation of the gene. Recent work demonstrates that Sp1 and NRF1 transcriptionally control this gene. Other studies reveal how the microRNA pathway and signaling are related to FMRP function through the metabotropic glutamate receptor. These studies provide new insights through which we can better understand the inactivation of the FMR1 gene and, in turn, the consequence of FMRP loss.