NOXA1 (NADPH oxidase activator 1) functions as a regulatory subunit that activates NOX1-based NADPH oxidase complexes to generate superoxide and reactive oxygen species (ROS) 1. NOXA1 operates as a moderate activator of NOX1, with lower efficiency than the canonical p67phox activator 2. The protein contains a PB1 domain and a single SH3 domain that modulates enzyme kinetics; while the SH3 domain is not strictly required for NOX1 activation, it critically regulates the rate of complex formation 3. NOXA1 can also activate NOX2 and NOX3, though with reduced efficiency compared to NOX1 2. NOXA1-mediated ROS generation is essential for invadopodia formation in colon cancer cells through c-Src-dependent phosphorylation at Tyr110, promoting extracellular matrix degradation 4. Clinically, NOXA1 overexpression correlates with radiotherapy resistance in colorectal cancer by suppressing ferroptosis through glutathione pathway regulation; targeting NOXA1 enhances radiosensitivity 5. NOXA1 also regulates macroautophagy and micromitophagy balance in schizophrenia pathophysiology via USF2-mediated transcriptional upregulation downstream of ERVWE1 6. Selective NOXA1 inhibition via peptide mimetics reduces NOX1-dependent ROS without affecting other NOX isoforms, showing therapeutic potential in vascular disease 7.