Cell signaling may be triggered by binding of proteases to distinct families of protease-activated receptors. The thrombin receptor or PAR1 and related receptors in the thrombin receptor gene family initiate cell signaling by a pathway that requires proteolytic cleavage of the N-terminal receptor ectodomain. Activated protein C (APC) cleaves PAR1 when bound to the endothelial protein C receptor (EPCR). Activation of cell signaling by proteases that bind to uPAR or LRP1 does not require proteolytic cleavage of the receptor. Many of the same cell-signaling pathways are activated downstream of PAR1, uPAR, and LRP1. Professional illustration by Kenneth X. Probst.