NADPH oxidase 5 (NOX5)

NADPH oxidase 5 (NOX5) is a member of the NADPH oxidase (NOX) family of enzymes whose primary function is to generate superoxide and other reactive oxygen species (ROS) by transferring electrons from NADPH to molecular oxygen[1][5][6]. NOX5 is a single polypeptide chain that uniquely contains four N-terminal EF-hand calcium-binding motifs, allowing for direct regulation by intracellular calcium levels; it does not require cytosolic subunits for activation, unlike other NOX family members[1][5]. The canonical structure includes six transmembrane domains and cytosolic FAD- and NADPH-binding domains[5]. NOX5 plays roles in cellular signaling, regulation of vascular tone, immune cell differentiation, reproductive functions (especially sperm motility), and is implicated in pathologies such as cancer, diabetes, hypertension, and cardiovascular diseases, largely due to ROS-mediated signaling and oxidative stress[1][2][4][7]. Overexpression or aberrant activation of NOX5 contributes to pathological redox imbalance, promoting disease progression[1][4][7]. Research interest in NOX5 as a potential therapeutic target is high, but human-specific challenges and lack of selective inhibitors currently limit clinical applications[6][8].

Other names

NOX5NADPH oxidase isoform 5Dual oxidase 5 (rarely used/incorrectly)EC 1.6.3.1 (enzyme classification)

Competitive inhibition of the NADPH-binding site (investigative compounds); Modulation of calcium binding to EF-hands (theoretical/investigative); Scavenging or reducing ROS downstream of NOX5 activity