A key event in the process of thrombus formation is the activation of integrin aIIbb3, which bridges adjacent platelets and mediates stable platelet adhesion to the ECM by binding to fibrinogen, fibronectin, von Willebrand factor and multiple ECM proteins. Outside-in signaling through the integrin further enhances aggregation, but also additional receptors on the platelet surface, as well as soluble mediators, are required for stable aggregation. Among these molecules is CD40L which, upon release from the platelet surface, supports stable formation of arterial thrombi by binding to integrin aIIbb3. The close proximity of platelets within the aggregates allows contact-dependent signaling via Rapamycin mTOR inhibitor interactions of receptors with their ligands on adjacent plasma membranes, like junctional adhesion molecules and ephrins/Eph kinases. CD84, a member of the signaling lymphocyte activation molecule family, is expressed on the surface of platelets and is also implicated to stabilize thrombi via homophilic interactions, but experimental evidence to support this hypothesis has not been provided so far. Members of the SLAM family are well recognized as important immunomodulatory receptors and are expressed on the surface of a wide variety of hematopoietic cells. CD84 is a type I transmembrane glycoprotein with an N-terminal ectodomain that comprises a membrane-proximal Ig constant domain and a membrane-distal Ig variable domain, which mediates the homophilic interaction between CD84 proteins. The C-terminal intracellular portion of CD84 bears two immunoreceptor tyrosine-based switch motifs, which can bind the intracellular adapters SLAM-associated protein and Ewing’s sarcoma activated transcript 2. Ligation of CD84 with a monoclonal antibody results in phosphorylation of the ITSMs and subsequent SAP recruitment, resulting in enhanced IFNc production and proliferation in T cells stimulated with low doses of anti-CD3 antibody. A study in CD84-deficient mice established CD84 as a functional co-receptor in lymphocytes that facilitates prolonged B cell:T cell interaction required for optimal germinal center formation. The effect of CD84-deficiency on platelet function has not been analyzed to date. However, several findings implicate that CD84 and its downstream signaling pathway may be of relevance in platelets. First, the cytoplasmic tail of CD84 is phosphorylated in response to platelet aggregation or upon antibody-mediated receptor crosslinking. Second, wild-type platelets, but not SAP-deficient platelets, are able to spread on immobilized CD84. Therefore, CD84 has been proposed to mediate contact-dependent signaling and contribute to thrombus stabilization. Third, a recent study from our laboratory demonstrated that CD84 receptor levels on platelets are tightly regulated by two distinct and independent proteolytic mechanisms upon platelet activation: shedding of the extracellular part by a disintegrin and metalloproteinase 10 and cleavage of the intracellular C-terminus by the protease calpain.