Protein synthesis is an indispensable process which accounts for a large proportion of the energetic resources of any living cells. Therefore, translational regulation must be tightly controlled. Such regulation is critical for protein biogenesis, folding, trafficking and degradation under stable and changing conditions. I will focus on the importance of hidden evolutionary signatures within the coding region of proteins that govern translational efficiency and dominate proteostasis in health and disease. I will discuss the notion of tRNA adaptation index (tAI) as an indirect measure for translation elongation efficiency. Specifically, I will show that proteins which must be localized to specific sites and organelles in cells evolved to support their optimal translation elongation rate. A link between an evolutionary signature within mRNAs and efficient management of protein production will be illustrated for the case of synaptic proteins and their family members. Neuronal communication is governed by the coordinated action of the synapse. In all organisms having a nerve system, the synapses are signified by the abundance of ion channels, cytoskeletal elements, ligand binding receptors, and secreted proteins. As such, the proteins composition is a showcase for an extreme demand of translational control. In the last part of the talk, I will extend the concept of translation regulation by illustrating the robustness of the translational machinery in view of post-translational regulation of miRNA in cells. I will present COMICS as a simulator that predict the global cell response to miRNA alterations, and illustrate the immunity of the translation apparatus to miRNA fluctuations. In summary, I will show that evolutionarily conserved design principles while often hidden are a strong determinant in the cell homeostasis in health and disease.