The papers assembled in this issue of ‘Bio logical Signals’ deal with eukaryotic initiation factor 5A (eIF-5A), which exists in both euka ryotic cells and archaea, but not in bacteria. This protein is the only cellular protein known to contain hypusine. Nature has committed two enzymes, deoxyhypusine synthase and deoxyhypusine hydroxylase, to specifically modify a single lysine residue of eIF-5A into hypusine, as illustrated in figure 1. This is no small commitment from Nature. Indeed, all the literature evidence indicates that eIF-5A, with its hypusine modification, is indispens able for cell survival and proliferation. As noted by Cohen in this issue, the discovery of the essentiality of hypusine in eukaryotic cells has demonstrated a unique and essential role for spermidine in the life of such cells, a fact that is not yet found in texts of biochemistry and cell biology. The highly conserved nature of the eIF-5A sequence from Methanococcus jannaschii to human (fig. 2), particularly near the hypusination site, futher confirms the im portance of hypusine formation. What re mains mysterious is that we do not know the cellular function of eIF-5A and the functional significance of hypusine modification. It is anticipated that, with most of the molecular