Altogether, our data show that Emilin-2, an ECM protein known to be involved in angiogenesis and tumor modulation [26–28], is a component of BM microenvironment involved in multiple functions in BM homeostasis, spanning from regulation of MSC differentiation to modulation of HSC pool and hematopoietic progenitor cell frequency. The gene discussed is EMILIN2; the disease is neoplasm.