Man1b1 cytoplasmic tail-mediated elimination of misfolded AAT is independent of Man1b1’s catalytic function. (A) Schematic of the catalytic-dead Man1b1 protein with the indicated amino acid mutation D463N. (B) Steady-state whole cell lysate Western blots of 293T E7 cells transfected with NHK and constructs encoding EV, WT, D463N, ∆1 to 54, or ∆1 to 54 D463N Man1b1. Western blots shown are representative of five independent experiments. (C) Graphic representations of NHK levels normalized to actin in whole cell lysates from the steady-state Western blot experiments shown in B. Data are reported as the mean ± SEM with statistical significance calculated by one-way ANOVA and Tukey’s multiple comparisons test. *P ≤ 0.05, ***P ≤ 0.001, ****P ≤ 0.0001, n = 5. (D) Steady-state whole cell lysate Western blots of 293T E7 cells transfected with ATZ and constructs encoding EV, WT, D463N, ∆1 to 54, or ∆1 to 54 D463N Man1b1. Western blots shown are representative of five independent experiments. (E) Graphic representations of ATZ levels normalized to actin in whole cell lysates from the steady-state Western blot experiments shown in D. Data are reported as the mean ± SEM with statistical significance calculated by one-way ANOVA and Tukey’s multiple comparisons test. ns, not significant. ****P ≤ 0.0001, n = 5.