The translationally controlled tumor protein (TCTP) is a small, multifunctional protein found in most, if not all, eukaryotic lineages, involved in a myriad of key regulatory processes. Among these, the control of proliferation and inhibition of cell death, as well as differentiation, are the most important, and it is probable that other responses are derived from the ability of TCTP to influence them in both unicellular and multicellular organisms. In the latter, an additional function for TCTP stems from its capacity to be secreted via a nonclassical pathway and function in a non-cell autonomous (paracrine) manner, thus affecting the responses of neighboring or distant cells to developmental or environmental stimuli (as in the case of serum TCTP/histamine-releasing factor in mammals and phloem TCTP in Arabidopsis). The additional ability to traverse membranes without a requirement for transmembrane receptors adds to its functional flexibility. The long-distance transport of TCTP mRNA and protein in plants via the vascular system supports the notion that an important aspect of TCTP function is its ability to influence the response of neighboring and distant cells to endogenous and exogenous signals in a supracellular manner. The predicted tridimensional structure of TCTPs indicates a high degree of conservation, more than its amino acid sequence similarity could suggest. However, subtle differences in structure could lead to different activities, as evidenced by TCTPs secreted by Plasmodium spp. Similar structural variations in animal and plant TCTPs, likely the result of convergent evolution, could lead to deviations from the canonical function of this group of proteins, which could have an impact from a biomedical and agricultural perspectives.