Extracellular HMGB1 activates multiple membrane receptors, including but not limited to receptor for advanced glycation end products, and TLR4, through which it contributes to the pathogenesis of lung injury, stroke, cancer, and so on (Andersson and Erlandsson-Harris, 2004; Kokkola et al., 2005; Muhammad et al., 2008; Sims et al., 2009; Yang and Tracey, 2010; Yang et al., 2010b; Schierbeck et al., 2011; Tolle and Standiford, 2013; Lv et al., 2016; Pandolfi et al., 2016). The gene discussed is TLR4; the disease is Stroke.