Myelofibrosis (MF) is a clonal blood cancer originating at the level of the hematopoietic stem cell (HSC) which is characterized by the acquisition of specific MPN driver mutations in janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) resulting in constitutive activation of JAK-STAT signaling (1). The gene discussed is MPL; the disease is myelofibrosis.