Eef2, or eukaryotic elongation factor 2, is a key ribosomal protein that catalyzes the elongation phase of protein translation, a fundamental process in all cells. It is ubiquitously expressed and is crucial for neuronal function among other biological processes. Post-translational modifications (PTMs) of eEF2, such as phosphorylation and methylation, can significantly influence mRNA translation dynamics [1,2,5,6].

In lung adenocarcinoma (LUAD), FAM86A-mediated methylation of eEF2 at K525 (eEF2K525me3) promotes protein synthesis and disease pathogenesis. Depletion of FAM86A in LUAD cells leads to 80S monosome accumulation and translation inhibition, and knockdown of FAM86A attenuates LUAD cell proliferation and xenograft growth in vivo [1].

In the context of depression, LPS-induced depression-like behaviors in mice are accompanied by reduced eEF2 activity, while fluoxetine treatment can reverse this and exhibit antidepressant effects, suggesting an involvement of eEF2 in the antidepressant mechanisms related to HDAC1-eEF2-associated neuroinflammation and synaptogenesis [2].

In megakaryocyte (MK) maturation and platelet production, lactate dehydrogenase A (LdhA) interacts with eEF2 in the cytoplasm, and inhibitors of LDHA that release eEF2 can enhance MK maturation and platelet production in vitro and in vivo [3].

In chronic infections by Pseudomonas aeruginosa, exotoxin A (EXOA)-driven ribosylation and inactivation of EEF2 promote ribotoxic stress and NLRP1 inflammasome activation in human airway and corneal epithelial cells [4].

In conclusion, Eef2 is essential for protein translation elongation and has far-reaching impacts on various biological processes and disease conditions. The use of gene knockout and other loss-of-function models, as seen in LUAD mouse models, has provided valuable insights into the role of Eef2 in cancer development. These findings highlight the significance of Eef2 in understanding disease mechanisms and potentially developing new therapeutic strategies.