Zn²⁺ homeostasis in megakaryocytes and platelets.Several Zn²⁺-responsive genes and transcription factors are expressed in megakaryocytes and involved in diverse processes, including granule biogenesis and platelet production. ZIP/ZnT transporters in megakaryocytes and platelets regulate Zn²⁺ influx/efflux and Zn²⁺ content in secretory granules, thereby facilitating Zn²⁺-dependent metabolic and signaling pathways. Granular-resident Zn²⁺ in platelets contributes to the activation of the coagulation cascade. The newly identified platelet Zn²⁺ transporter TMEM163 (also called ZnT11) is located in the δ-granule membrane and regulates the biogenesis of δ-granules in megakaryocytes. BLOC-1, BLOC-2, and AP-3 are involved in this process and transport TMEM163 from early endosomes to perinuclear δ-granules and late-endosome–positive compartments.