Thus, while cytoplasmic full-length FMRP isoforms are involved in the control of protein synthesis, we speculate that future studies investigating the role of nuclear isoforms in regulating the activity of the proteasome may reveal how the cytoplasmic and nuclear FMRP isoforms function in a compensatory pathway to maintain cell homeostasis, and possibly also further extend our understanding the molecular pathways underlying the role of nFMRP in DNA damage signaling by regulating the activity of the nuclear proteasome, whose alteration may contribute to the pathophysiology of FXS. Here, FMR1 is linked to fragile X syndrome.