Septins are a family of filamentous GTPases with 13 members in mammals. These proteins form oligomers and complexes with other proteins to serve as multi-molecular scaffolds and recruit components of signaling pathways. In platelets, septins are highly expressed and are possibly involved in vesicle trafficking. Dysregulation of septins leads to a variety of human diseases and amongst others to bleeding disorders. Originally, our group cloned 4 of these septins (SEPT4, SEPT5, SEPT8, SEPT11) and investigated septin expression and septin interaction with other proteins. We cloned SEPT5 as one of the first human septins and described the expression of other septins in human endothelial cells and platelets. In particular, we showed that some septins (SEPT4, 5, and 8) are localized around the platelet α-granules and move to the platelet surface after activation, suggesting a role of for these septins in platelet function. In this context we identified the first patient with a SEPT5-defect suffering from life-threatening bleedings due to co-deletion of SEPT5 and GPIbβ (encoding for the subunit of the platelet von Willebrand factor receptor GPIb/IX). This boy showed a platelet secretion defect and developmental retardation. To identify the impact of septins in bleeding disorders and to contribute to a better understanding of septin physiology, we perform extensive platelet function analyses in septin-knockout mouse models.