One of the largest ribosomal proteins, uL4 is best known for its role in forming a so called constriction of the nascent peptide tunnel of the ribosome. One remarkable feature of this constriction is that its gradually getting more pronounced upon transition from bacteria to eukaryotes. Thus, in bacteria ...; in archaea, ..., and in eukaryotes, .... There is a growing evidence that more prominent constriction in eukaryotes may contribute to resistance of the eukaryotic ribosomes to macrocodes: current models suggest (although speculatively) that macrocodes may penetrate the ribosome from the cytosol-exposed side of the large ribosomal subunit through the nascent peptide tunnel. In this model, the narrower constriction of eukaryotic ribosomes does not allow drugs to reach their binding site in the ribosome. One experiment supporting this model shows that insertion of additional four amino acids into protein uL4 ("humanizing" protein uL4) indeed confers resistance of bacterial ribosome to macrolide antibiotics.