One characteristic type of the common somatic mutations causing myeloproliferative neoplasias is the frameshift mutation of the calreticulin gene that leads to proteins of abnormal structure. The pathologic protein induces novel cell biological processes that are fundamental to the onset and maintenance of myeloproliferative diseases. In this review, an insight is provided into these processes, aiding better understanding of the underlining pathobiological processes and eventually to more effective therapy in the future.