The amount of hUPF1 is critical for neuroprotection. (A) mApple levels were unrelated to survival (n = 193, plinear = 0.94, pnonlinear = 0.53), but increasing amounts of TDP43(A315T)-mApple (B) magnified hazard (n = 164, plinear = 1 × 10−9, pnonlinear = 0.01). In control neurons (C), hUPF1-EGFP levels and hazard were linearly related (n = 193, plinear = 1 × 10−6, pnonlinear = 0.2), indicative of dose-dependent toxicity. In TDP43(A315T)-mApple transfected neurons, low levels of hUPF1-EGFP (D) reduced hazard, whereas high levels were toxic (n = 164, plinear = 0.005, pnonlinear = 0.3). (E) Splines for hUPF1-EGFP in neurons expressing mApple or TDP43(A315T)-mApple emphasize hUPF1’s neuroprotective properties at low levels. (F) Neurons expressing TDP43(A315T)-mApple and hUPF1-EGFP were separated into quintiles based upon GFP intensity, and survival was analyzed by LFM. *P < 0.04; ns, not significant, Cox hazards analysis. Dotted lines in A–D, 95% confidence interval.