Notably, the activation of the CCL4L2‐VSIR pathway contributes to T cell exhaustion in severe cytokine storms, which is associated with poor prognosis in COVID‐19.[27] Targeting CCL4L2‐VSIR could inhibit various inflammatory diseases, autoimmune diseases, and tumor metastasis.[42, 43, 44, 45] Here, we revealed that abnormal activation of the CCL4L2‐VSIR axis in the GI tract ultimately drives non‐canonical IBD in GSD‐Ib. Here, VSIR is linked to inflammatory bowel disease.