CPOX (coproporphyrinogen oxidase) catalyzes the aerobic oxidative decarboxylation of coproporphyrinogen-III to protoporphyrinogen IX, representing the sixth step in heme biosynthesis [UniProt]. The enzyme functions as a mitochondrial intermembrane space protein and homodimer involved in heme B biosynthetic pathways. Biallelic CPOX mutations cause harderoporphyria, a rare porphyria characterized by coproporphyrinogen oxidase deficiency 1. Heterozygous mutations result in hereditary coproporphyria (HCP), an acute hepatic porphyria presenting with severe abdominal pain, neurovisceral manifestations, and cutaneous symptoms 2. HCP patients exhibit elevated urinary and fecal coproporphyrin excretion; genetic testing for CPOX pathogenic variants confirms diagnosis following positive biochemical screening 2. CPOX protein levels critically regulate protoporphyrin IX fluorescence in glioma cells, correlating with proliferative activity 3. The BALB.NCT-Cpox nct mouse model demonstrates that CPOX mutations cause microcytic anemia, neuromuscular dysfunction, and sex-dependent hepatic/cutaneous pathology including nonalcoholic steatohepatitis 45. Recent evidence indicates CPOX mutations impair mitochondrial steroidogenic enzyme function, causing primary adrenal insufficiency alongside classic porphyria features 1. Genome-wide association studies identify CPOX as a genetic determinant of cerebrospinal fluid Alzheimer's disease biomarker levels 6. Management of acute HCP attacks involves intravenous hemin and prophylactic therapy for recurrent episodes 2.