G6PD suppresses thrombopoiesis via interfering with TMOD3-mediated actin dynamics.

G6PD deficiency increases platelet counts by enhancing proplatelet formation through disrupted actin dynamics in humans and mice.

• Why it matters: Understanding G6PD's role in platelet biology is important because its deficiency is common worldwide, yet its specific function in thrombopoiesis remains unclear, limiting potential therapeutic strategies.
• What they did: The study examined human patients and murine models, revealing that G6PD deficiency leads to elevated platelet counts via increased proplatelet formation, and identified a mechanism involving G6PD's interaction with TMOD3 affecting actin rearrangement.
• The result: A G6PD-derived peptide, GC2P2, was shown to enhance the G6PD-TMOD3 interaction, significantly suppressing thrombopoiesis both in vitro and in vivo, suggesting new avenues for controlling platelet production.