In this report, we show that: i) mice deficient in LMAN1 exhibit thrombocytopenia; ii) mice with hepatocyte-specific Lman1 deletion exhibit thrombocytopenia, while mice with hematopoietic Lman1 deletion do not; iii) plasma TPO level is reduced in Lman1–/– compared with WT littermate controls; iv) TPO mRNA is unchanged in Lman1–/– hepatocytes; v) TPO protein accumulates intracellularly in LMAN1-deficient cells; and vi) TPO and LMAN1 physically interact. This evidence concerns the gene TPO and Thrombocytopenia.