Dihydropyrimidinase-related protein 2/collapsin response mediator protein 2 (DPYL2/CRMP2) binds to tubulin heterodimers to promote microtubule formation and stability, resulting in axonal growth and neuronal polarity . Cyclin-dependent kinase 5 (Cdk5) and glycogen syntheses kinase 3β (GSK-3β) regulate DPYL2 activity . The phosphorylation of DPYL2 by GSK-3β can inactivate DPYL2 function . DPYL2 is phosphorylated at Ser522 by Cdk5 and subsequently at Ser518, Thr514, and Thr509 by GSK-3β in brain tissue from human AD patients and in some mouse models of AD . Aβ25–35-induced impairment of cognitive function and LTP was not observed in DPYL2 phosphorylation-deficient knock-in mice, in which Ser522 of DPYL2 was replaced with alanine , suggesting that the phosphorylation of DPYL2 at Ser522 was associated with Aβ25–35-induced cognitive memory deficit and impairment of LTP. Indeed, our findings showed that phosphorylated DPYL2 was increased in the hippocampus and cortex of STZ-treated mice. Taken together, it is suggested that phosphorylated DPYL2 plays an important role in diabetes-induced dementia. Interestingly, DPYL2 was identified from two phosphoprotein spots on 2-DE gels stained with Pro-Q Diamond staining in the hippocampus. The shift in the position of these phosphoprotein spots may imply translational modifications such as phosphorylation, acetylation, and degradation.