Furthermore, we uncovered evidence through use of the irreversible inhibitor OG-L002 that 2D cytotoxicity and proliferation assays may be insufficient to determine Ewing sarcoma response to LSD1 inhibition.<h4>Significance</h4>In this study, we address a long-standing question in the field surrounding LSD1 and define the distinct enzymatic and nonenzymatic functions of LSD1 in Ewing sarcoma. The gene discussed is KDM1A; the disease is Ewing sarcoma.