Through the integration of single-cell transcriptomics and spatial transcriptomics, a recent study has provided compelling evidence to show that hepatocyte growth factor activator (HGFAC) Arg509His (R509H), a risk variant for Crohn’s disease activated by thrombin protease activity, restricts fibroblast-mediated tissue reestablishment in the inflammatory intestine on account of impairing proteolytic activation of the growth factor macrophage-stimulating protein (MSP). The gene discussed is MST1; the disease is Crohn disease.