Structural maintenance of chromosomes hinge domain containing 1 (Smchd1) is a noncanonical SMC protein that mediates long-range repressive chromatin structures. Smchd1 is required for the maintenance of X-chromosome inactivation in female cells and repression of imprinted and clustered autosomal genes. Mutations in SMCHD1 have been linked to human diseases, facioscapulohumeral muscular dystrophy (FSHD) and bosma arhinia and micropthalmia syndrome (BAMS). Given the potential of SMCHD1 as a therapeutic target and its ubiquitous expression pattern, it is important to understand its function across different tissues. In mice, Smchd1-null females die around E10.5 and show failed X-chromosome inactivation, so here we have used a conditional mouse model to investigate the role of Smchd1 specifically in haematopoiesis. Blood cell-specific deletion of Smchd1 did not lead to haematological malignancy in mice that were monitored for over one year. However, both male and female mice with Smchd1 deleted in the blood system have an altered haematopoietic stem and progenitor cell (HSPC) compartment revealed by reduced repopulating capacity in competitive bone marrow transplantation assays compared to controls. Gene expression profiling of Smchd1-deleted haematopoietic cells revealed over-expression of known Smchd1 targets, including imprinted genes and clustered protocadherins, as well as additional genes with known roles in haematopoietic stem cell function, but did not show a widespread upregulation of X-linked genes. Future plans are aimed at identifying the molecular changes in HSPCs caused by the absence of Smchd1 and how they cause the defect in the HSPC pool.