Pharmacological inhibition of STING ameliorates neurological disease of NGLY1 deficiency. (A) Experimental workflow of treatment of iNgly1^−/− mice. (B) Neurological deficit score of Ngly1^fl/fl (n = 7 mice) and iNgly1^−/− mice treated with STING inhibitor VS-X4 (n = 8 mice) or vehicle control (n = 9 mice). Data were shown as median ± 95% CI. Mann–Whitney U test. **P < 0.01; ***P < 0.001; ns, not significant. (C) Disease onset (disease incidence in the month when kyphosis score reaches 2) of Ngly1^fl/fl (n = 7 mice) and iNgly1^−/− mice treated with STING inhibitor VS-X4 (n = 8 mice) or vehicle control (n = 9 mice). Log-rank (Mantel–Cox) test. *P < 0.05. (D) IHC staining of calbindin in cerebella of iNgly1^−/− mice treated with the STING inhibitor VS-X4 or vehicle control for 3 mo. Scale bar, 500 μm (upper), 100 μm (lower). (E) Quantification of Purkinje cell number of iNgly1^−/− mice treated with the STING inhibitor VS-X4 or vehicle control for 3 mo. One-way ANOVA with Bonferroni’s multiple comparisons test. *P < 0.05; **P < 0.01.