The cell surface orchestrates plasminogen activation through the concomitant binding of plasminogen and plasminogen activators to specific receptors. In this issue, Miles and colleagues describe their detailed phenotypic characterization of mice deficient in Plg-RKT, a key plasminogen receptor expressed in numerous tissues, but highly expressed by proinflammatory macrophages. The analysis provides critical and surprising new insights into the biology of this receptor. This article is protected by copyright. All rights reserved.