Thrombospondin-1 (TSP-1) is a secreted homotrimeric protein that regulates a wide range of cellular functions including their interactions with other cells and with the extracellular matrix (ECM). TSP-1 counteracts the angiogenic, hypotensive, and anti-thrombotic effects of nitric oxide (NO). It binds and neutralizes VEGF, blocks VEGF R2 signaling on vascular endothelial cells (EC), and destabilizes adhesive contacts between EC. TSP-1 also plays an important role in wound repair and tissue fibrosis by binding latent TGF-beta and inducing release of the active cytokine from the latency associated peptide (LAP). TSP-1 dampens adaptive immune responses by inducing the differentiation of regulatory T cells and inhibiting TCR signaling. In the nervous system, it promotes excitatory synapse formation and supports the integration of neural progenitor cells into the olfactory bulb.