Warfarin, a juggler's demise.

Warfarin, an anticoagulant therapy used by millions worldwide, inhibits vitamin K epoxide reductase complex subunit 1 (VKORC1), thereby dampening the carboxylation and the procoagulant potential of vitamin K–dependent coagulation factors. However, the detailed molecular mechanism by which warfarin inhibits VKORC1 remains the subject of debate. In this issue of , Rishavy et al puts this issue to rest by demonstrating that warfarin inhibits VKORC1 via a mechanism termed “the uncoupling of VKORC1.” The uncoupling of VKORC1 is significant because it highlights a potential cooperation of VKORC1 with a second warfarin-resistant vitamin K quinone reductase, thereby explaining how considerable carboxylation can proceed despite the presence of warfarin, and this may have direct implications for warfarin dosing in patients.