Inhibition of RUNX1 activity caused a reduction in fibroblast activation, contraction, extracellular matrix components, and proliferation rates, including a reduction in SFRP4, LUM, and COL1A1.<h4>Conclusions</h4>This study is the first to demonstrate a potential role for RUNX1 in the pathogenesis of SSc dermal fibrosis. Here, LUM is linked to systemic sclerosis.