JAK-targeted therapies, such as the first-in-class JAK1/2 ATP competitive inhibitor ruxolitinib7–9, were introduced a decade ago for the treatment of myeloproliferative neoplasms (MPN) driven by JAK/STAT signaling activating mutations in JAK210, CALR11 or MPL12. The gene discussed is JAK1; the disease is myeloproliferative neoplasm.