To explore the potential mechanisms regulating the effects of icaritin on U266 cells, and determine if anti-MM activity of icaritin is related to the inhibition of IL-6 mediated autocrine loop, we examined several major oncogenic signaling pathways, including IL-6, JAK2, STAT3, and two members of mitogen-activated protein kinase (MAPK) family: JNK and ERK. This evidence concerns the gene WNK2 and Miyoshi myopathy.