G6b-B is highly expressed in mature MKs and G6b-B KO and loss-of-function mice show a severe macrothrombocytopenia resulting from impaired proplatelet formation and platelet production, which is accompanied by an increase in MK numbers in the bone marrow (Geer et al., 2018; Mazharian et al., 2012). Here, we provide first evidence for a potential role of perlecan in regulating MK function by demonstrating that G6b-B-deficient, but not WT, MKs increase their size in the presence of the HS side-chains of perlecan, indicating cellular activation. The gene discussed is HSPG2; the disease is Macrothrombocytopenia.