It is not yet clear how Arc regulates these cell-wide responses to long-term changes in activity that oppose the changes seen in LTP and LTD. Although increased AMPAR endocytosis might explain a homeostatic response to increased activity, Arc appears to be required for both down- and up-scaling [65]. Even more ambiguous is how Arc mediates the lasting response to short-term stimuli that results in LTP or LTD and, concurrently or sequentially, responds to long-term tonic changes in activity through effects on scaling. Given the difficulty of reconciling the disparate data on Arc’s role in plasticity, Arc has been proposed to subserve more than one function, depending on its location in the cell and its interaction partners [18].