The structural insights into the JAK activation process gained through the cryo-EM structures of dimerized mJAK1, both past8 and present, and complemented by structural predictions from AlphaFold, should provide new drug discovery opportunities to treat chronic inflammation, autoimmune diseases, myeloproliferative neoplasms, and cancers arising from aberrant activation of JAK-STAT signaling pathways. Here, SOAT1 is linked to myeloproliferative neoplasm.