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NADPH oxidase 2 catalytic subunit (NOX2, also known as gp91^phox^) is the principal catalytic component of the phagocyte NADPH oxidase complex. It is a transmembrane flavocytochrome found in neutrophils and other immune cells, where it functions to generate superoxide anion (O_2^–^) by transferring electrons from cytosolic NADPH across the membrane to molecular oxygen. The protein forms a heterodimer with p22^phox^ (the small subunit), together constituting the membrane-bound flavocytochrome b_558_. Activation of the NOX2 complex requires assembly with cytosolic subunits (p47^phox^, p67^phox^, p40^phox^) and a small GTPase Rac1/Rac2, resulting in a rapid "respiratory burst" of superoxide to kill ingested microbes as part of innate immunity[2][3][4][6]. Loss or mutations of gp91^phox^/NOX2 cause chronic granulomatous disease, a rare primary immunodeficiency characterized by severe recurrent infections. Pathological NOX2 activation is also implicated in vascular and inflammatory diseases due to excessive ROS production[3][4]. Drugs such as naloxone and other NOX2 inhibitors are under investigation for their ability to modulate immune and inflammatory responses[5].
Inhibition of superoxide production via direct interaction with gp91^phox^ subunit (e.g., naloxone)[5]
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