TARDBP and proteostasis deficiencies: Yet, despite the apparent promise of decreased PFKP as a TDP-43 loss-of-function marker, glycolysis is hypothesized to be a compensatory mechanism in ALS, and in human ALS spinal cord tissue with TDP-43 proteinopathy, PFKP levels were found to increase rather than decrease compared to those in controls (Manzo et al., 2019).