The mammalian ribosome is a complex structure composed of four ribosomal RNAs (rRNAs) and 79 ribosomal proteins (RPS). It is responsible for catalysis of protein synthesis, and as such plays a key role in controlling cell growth, proliferation and differentiation. Most steps in ribosome biogenesis are temporally and spatially organized within the nucleolus, where the 45S rRNA precursor is transcribed, processed, modified and assembled with 5S RNA and RPS to generate the mature 40S and 60S ribosomal subunits (Fig. 1). RPS participate in additional steps during ribosome biogenesis in the nucleoplasm and the cytoplasm, such as transport of ribosomal precursors, stabilization of ribosome structure and regulation of mRNA translation (Fig. 1). Ribosome biogenesis involves exceptionally high energy consumption and errors in this process can result in quantitative or qualitative defects in mRNA translation, which could lead to the development of a wide variety of pathological conditions. In addition to their conventional role in ribosome biogenesis and protein synthesis, some RPS appear to possess extraribosomal functions in diverse biological processes.