aPC is an anticoagulant serine protease that inactivates coagulation factors Va and VIIIa. In addition to its anticoagulant activity, aPC can induce anti-inflammatory cell signaling via cleavage of PAR-1 at arginine 46 (R46). Activation of PAR-1 by aPC triggers “biased” signaling via β-arrestin, phosphoinositide 3-kinase (PI3K), and AKT, leading to inhibition of NF-κB and mTORC1, and suppression of NLRP3 inflammasomes. In contrast, thrombin cleaves PAR-1 at arginine 41 (R41) and stimulates proinflammatory signaling pathways (not shown). Professional illustration by Somersault18:24.