**4. Conclusions**

The discovery of *MYSM1* mutations in patients with a hereditary developmental and bone marrow failure syndrome raises strong interest in understanding the MYSM1-regulated checkpoints in mammalian physiology and the underlying molecular mechanisms of MYSM1 activity in these systems. Over the past decade, research in mouse models has provided numerous important insights, although many unanswered questions and opportunities for discoveries remain. The role of MYSM1 as a transcriptional regulator of hematopoiesis and immune cell development has been most extensively studied, although the diverse findings remain to be consolidated and reconciled. In particular, genome-wide characterization of MYSM1-regulated genes in the relevant hematopoietic cell types promise to provide many new insights into MYSM1 functions. The recently discovered role of MYSM1 in the regulation of signal transduction in the cytosol is highly interesting, however, research to date has focused only on the signaling pathways of innate immunity and primarily in macrophages. Furthermore, except for several recent insightful studies, MYSM1 functions and mechanisms of action beyond hematopoiesis and immunity remain poorly characterized. We expect that many new studies in coming years will address these and other outstanding questions, providing insights into the basic molecular mechanisms regulating mammalian development and physiology and further understanding into the disease pathology in *MYSM1*-deficiency in humans.

**Author Contributions:** Y.L., Y.H.L., J.T., H.W., D.L., A.N. contributed to manuscript preparation. A.F. contributed to manuscript preparation and the Figures. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was funded by the Canadian Institutes of Health Research (CIHR, Project Grant PJT-153016, Operating Grant MOP-123403), and supported by the Canadian Foundation for Innovation (CFI). A.N. is a Canada Research Chair Tier II in Hematopoiesis and Lymphocyte Di fferentiation. A.F. was a recipient of the Frederick Banting Tri-Council Scholarship, and was previously supported by FRQS Masters Training Studentship and the Max & Jane Childress Entrance Fellowship from the Department of Physiology of McGill University. Y.L. was supported by the Richard Birks Fellowship from the Department of Physiology of McGill University. Y.H.L. is a recipient of the Cole Foundation Studentship, and was previously supported by the Frederick Banting Tri-Council Graduate Scholarship. H.C.W. is a recipient of the Fonds de Recherche du Québec Santé (FRQS) Masters Training Studentship. D.L. was supported by the Fonds de Recherche du Québec Santé (FRQS).

**Conflicts of Interest:** The authors declare no conflicts of interest.
