Forced expression of Id2 but not Id2-S14A augmented αK40 acetylation and restored MT stability facilitating axonal growth in the hippocampus of 5X-FAD despite elevated Sirt2 activity, suggesting that upregulation of Id2 may be a novel strategy to improve MT dynamics in neurodegenerative diseases in which MT disorganization is implicated in pathogenesis. Here, SIRT2 is linked to neurodegenerative disease.