One reason to suspect that Arc has additional yet-to-be discovered functions is that, in addition to being localized to dendrites, Arc is also enriched in the nucleus [11,12]. Arc interacts with the nuclear matrix protein bspectrinIVS5 to promote the formation of promyelocytic leukemia nuclear bodies (PML-NBs) [11]. PML-NBs are involved in brain development [67] and regulate many nuclear functions, such as transcription and mRNA export [68,69]. Changes in these nuclear functions would have cell-wide effects, making this an attractive mechanism for mediating functions such as homeostasis. However, the function of PMLNBs varies widely between cell types and has not been investigated in neurons, so it is not yet known whether modifying PML-NB formation affects synaptic plasticity. Additionally, the molecular mass of Arc is near the size cutoff for passive diffusion into the nucleus through the nuclear pore complex, so it is not clear if the high level of Arc nuclear localization is due to active transport or simple diffusion and nuclear retention. Clearly, more research s needed to determine exactly how Arc functions in TP, LTD and scaling and how the protein is localized to different cellular regions to mediate these effects.