Here, we report the identification of heterozygous LOF variants in SOCS1, a negative regulator of the JAK-STAT signaling pathway, as the cause of refractory intestinal inflammation in two unrelated adult patients with Crohn’s disease-like disease and leiomyositis-related CIPO respectively, both successfully put in remission by targeted therapy. The gene discussed is SOAT1; the disease is chronic intestinal pseudoobstruction.