MPIG6B encodes G6b-B, a megakaryocyte-specific immunoreceptor containing two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that functions as an inhibitory receptor 1. G6b-B plays an essential role in megakaryocyte differentiation and platelet homeostasis by regulating early lineage commitment and proplatelet release 1. The receptor modulates megakaryocyte development through thrombopoietin signaling and maintains expression of GATA-1, a critical megakaryocytic transcription factor 1. Loss-of-function MPIG6B mutations in humans cause congenital thrombocytopenia accompanied by myelofibrosis, anemia, and organomegaly 23. In myelofibrosis patients with thrombocytopenia, reduced G6B expression correlates with impaired megakaryocyte maturation and accumulation of proinflammatory megakaryocytes, which produce elevated TGFβ1 and YKL-40 that further suppress normal development 4. G6B represents a potential therapeutic target in both inherited G6B deficiency and acquired myelofibrosis-associated thrombocytopenia 5. Clinical evidence demonstrates that allogeneic hematopoietic stem cell transplantation effectively reverses disease manifestations in patients with MPIG6B mutations 2.