14-3-3θ, a novel player in TDP-43 pathophysiology: Implications for ALS/FTD.

In this issue of Neuron, Ke et al. 1 report a novel non-canonical interaction between 14-3-3θ and TDP-43 that impacts loss-of-function and gain-of-toxic pathology in TDP-43 proteinopathies. The authors further provide proof of principle for a 14-3-3θ-targeted gene therapy to reduce TDP-43-induced deficits in transgenic TDP-43 mutant mice.