The NK Motif And AnKyrin Repeat Domain 1 (KANK1) gene protein plays a role in the control of cytoskeleton formation by regulating actin polymerization. A t(5;9) translocation resulting in a fusion of the platelet-derived growth factor receptor beta gene (PDGFRB) and KANK1 was detected in a patient with myeloid neoplasm (MN) characterized with severe thrombocythemia[2]. The protein is thought to have a tumour suppressor function, as its expression is downregulated or missing in several tumor tissues, while over-expressing the protein was reported to inhibit the proliferation of tumor cells in solid cancer models [3-5]. We established a novel germline loss of heterozygosity (LOH) mutation encompassing the KANK1 gene in a young Myelodysplastic syndrome (MDS) patient and his healthy father, with no additional MDS-related mutations or chromosomal abnormalities. Clinical investigation suggested development of MDS following severe infection, likely triggered by an autoimmune mechanism. The Kank1-/- mice remained healthy and did not develop any hematological abnormality. loss of Kank1 expression led to alteration in the cologenic and proliferative potential of murine BM cells and decrease in HSPCs population frequency. Comprehensive marker expression analysis of lineage cell populations indicated a role for Kank1 in lymphoid cells differentiation. Total protein analysis suggests the involvement of Kank1 in BM cells’ cytoskeleton formation and mobility.