A recent clue to the activation mechanism comes from the study of multiple myeloma, a disease in which malignant plasma cells extravasate throughout the bone marrow of affected patients, and a unique response of the cells when CD138 (syndecan-1) is targeted by heparanase (HPSE), an HS-degrading endoglucuronidase (60). The gene discussed is SDC1; the disease is plasma cell myeloma.