Cell size plays an indirect role in cell proliferation, as cells must double in size before dividing. Cell size is largely determined by the activity of RNA polymerase I that controls ribosomal RNA synthesis and ribosome biogenesis. The type 1 insulin-like growth factor receptor (IGF-IR) and its docking protein, insulin receptor substrate-1 (IRS-1) control, in a non-redundant way, about 50% of cell and body size. This is certainly true in mice, flies and cells in culture, but also probably in higher mammals. Interestingly, the insulin receptor (InR) cannot substitute for the IGF-IR in controlling cell size. This is probably due to the fact that the IGF-IR is more effective than the InR in translocationg to the nuclei IRS-1, which then binds UBF1, one of the proteins that regulate RNA pol I activity.