Coagulation factor XI circulates in plasma mostly as a non covalent complex with high molecular weight kininogen (HK), encoded by the KNG1 gene (depicted here as KNG1(19–644)). HK anchors FXI to surfaces, facilitating its activation by factor FXIIa (Renné T et al., 2002; Bar Barroeta A et al., 2022; Singh PK et al., 2022; Li C et al., 2023; Mohammed BM et al., 2024). The FXI:HK complex formation is mediated by domain 6 (D6) of KNG1(19 644) and the apple 2 (A2) and A3 domains of FXI (Singh PK et al., 2022; Bar Barroeta A et al., 2022; Li C et al., 2023; Mohammed BM et al., 2024). While the interaction between FXI and HK (19 644) is not essential for hemostasis, it contributes to contact activation induced, FXII mediated clotting both in vitro and in vivo (Mohammed BM et al., 2024). HK on cells (endothelial cells, platelets) serves as a binding site, putative receptor for FXI (Shariat-Madar Z et al., 1998). FXI binding to endothelial cells with HK is zinc ion dependent; FXI will bind endothelial cells in the absence of HK, but to a much lesser extent.