PDK1 and Thrombocytopenia: The deletion of S1P receptor 1 results in severe thrombocytopenia.50 Phosphoinositide-dependent protein kinase 1 (PDK1), a key regulator of the phosphoinositide 3-kinase/Akt pathway, plays a crucial role in thrombin-induced platelet activation and arterial thrombosis formation.51 Loss of PDK1 in MKs disrupts actin cytoskeleton organization, reduces podosome formation, and impairs interactions between MKs and sinusoids, leading to MK hyperplasia and extramedullary thrombopoiesis.52