In this issue of Blood, Kondreddy et al reveal a novel endothelial cellular pathway that directly promotes inflammatory-mediated venous thrombogenesis, for which an exogenous nonanticoagulant inhibitor is effective. This pathway involves the Gab2 protein (Grb-associated binder to adaptor signaling protein), which is downstream from interleukin β-1 (IL-β1) signaling and through which the pathway confers MALT1 activation as well as CARAMA-3 phosphorylation. This mediates intracellular activation of Rho and the NF-κB–mediated processes that drive thrombogenesis.