A) For decades, the gold standard approach for isolating RPs in the context of intact, functional, ribosomes has been sucrose gradient centrifugation. B) Affinity purification is a powerful means of identifying differential RP association with complexes, however it cannot definitively say whether an RP is resident in a ribosome or represents an extra-ribosomal population of the RP. C) A combined approach whereby affinity purification is performed on sucrose gradient fractions allows the advantages of affinity purification to be applied to samples where the RP is known to be ribosome-resident. D) Heterogeneity amongst ribosomal protein modifications is a promising new area of research, and the methods required to explore this are an extension of those for identifying changes to RP association. Protease-digested peptides from sucrose gradient fractions or affinity purification can be enriched for a particular PTM of choice, either individually, or serially whereby the flow-through of one enrichment is applied to the next enrichment process.