MPIG6B (megakaryocyte and platelet inhibitory receptor G6b), also known as G6b-B or C6orf25, is a lineage-specific immunoreceptor tyrosine-based inhibition motif (ITIM)-containing receptor belonging to the immunoglobulin superfamily. It is predominantly expressed on megakaryocytes and platelets, where it acts as a critical negative regulator of hematopoietic lineage differentiation, megakaryocyte maturation, and platelet production. G6b-B constitutively associates with the tyrosine phosphatases Shp1 and Shp2 to inhibit signaling from ITAM-containing receptors such as GPVI and CLEC-2, thereby attenuating platelet aggregation and activation. Loss-of-function mutations in MPIG6B in humans cause autosomal recessive congenital macrothrombocytopenia with focal myelofibrosis, characterized by severe thrombocytopenia, anemia, and bleeding diathesis.