and repair, as indicated by blood cellular markers of increased endothelial injury and decreased endothelial repair. These markers of endothelial injury were significantly associated with disease severity and improved following SMN restoration treatment in Cultured endothelial cells from SMA patients. Finally, we demonstrated autonomous defects in angiogenesis and blood vessel formation, secondary to SMN deficiency in cultured human and mouse endothelial cells, as the underlying cellular mechanism of microvascular pathology. Our cellular and vascular biomarkers findings strongly indicate microvasculopathy as a novel and fundamental feature of SMA. Our finding provides mechanistic insights into previously described SMA microvascular complications, which may contribute to the thrombotic microangiopathy complications following AAV gene therapy, and highlight the novel functional role of SMN in the periphery.