Myeloma plasma cells, as depicted by antibody secretion, produce SHH through an unknown mechanism. They can secrete it via Disp1 and then use it through their PTCH receptors to allow for activation of SMO (at a cilia) to activate Gli1. Gli1 regulates proliferation and survival through target genes CCND1 and Bcl-2 and activates a negative feedback loop through he activation of PTCH expression. Targeting the pathway can be achieved through SMO antagonists (cyclopamine, NVP-LDE255) or agonists of liver X receptors (LXRs). Professional illustration by Patrick Lane, ScEYEnce Studios.