NOS3 is an important nitric oxide (NO)-generating enzyme of the vasculature that is regulated by interactions with caveolin-1, Ca2+-calmodulin, HSP90 and NOSIP. It catalyzes the production of nitric oxide (NO), a key regulator of blood pressure, vascular remodeling, and angiogenesis. NOSIP modulates this activity by promoting the translocation of NOS3 from the plasma membrane to intracellular sites, which in turn inhibits NO synthesis. The activity of NOS3 is regulated by phosphorylation at multiple sites. The two most thoroughly studied sites are the activation site Ser1177 and the inhibitory site Thr495.