Protein synthesis involves initiation, elongation, and termination. A number of studies show that translation elongation is highly regulated and is the most energy-intensive process, which controls the efficiency and accuracy of protein synthesis. In the elongation process, eukaryotic elongation factor 2 (eEF2) binds to the ribosome to induce its conformation change and promotes the translocation of the tRNAs by hydrolyzing guanosine triphosphate, which then allows the next AA-tRNA to enter the A site for translation elongation. The activity of eEF2 is negatively regulated by its kinase eEF2K that phosphorylates eEF2 at threonine-56 (Thr56). Dysregulation of elongation is the core of the pathogenesis of tumorigenesis and neurodegeneration. Thus, eEF2/eEF2K as a potential therapeutic target has attracted more and more attention (Knight et al., 2020). In a recently published work, we identified that the intellectual disability related protein, polyglutamine-binding protein 1 (PQBP1), is a novel regulator that binds directly with eEF2 and affects its phosphorylation (Figure 1; Shen et al., 2021).