Although the Hh signaling pathway has been associated with cancer stem cell generation, and both the CD138+19,20 and CD138–18 cell populations secrete Hh ligands that activate autocrine signaling in MM, we have identified a primate-specific mechanism of Hh pathway activation in MM through enhanced transcriptional activation of GLI1 following Alu-dependent ADAR1-mediated RNA editing. Here, GLI1 is linked to Miyoshi myopathy.