Gain-of-function variants can potentially be treated using a variety of JAK1 or JAK1/2 inhibitors that are clinically available for the treatment of rheumatoid arthritis, myeloproliferative disease, and inflammatory bowel disease [77, 78] since GP130 relies on the recruitment of JAK1 and JAK2 for downstream signaling. Here, JAK2 is linked to inflammatory bowel disease.