Sivaraj, Majev et al. demonstrate that the inactivation of Lats2 in endothelial cells triggers the upregulation of serum response factor and endothelial-to-mesenchymal transition, leading to myofibroblast formation, bone marrow fibrosis, osteosclerosis, impaired bone marrow function and extramedullary hematopoiesis. This evidence concerns the gene LATS2 and osteosclerosis.