PPOX (protoporphyrinogen oxidase) catalyzes the 6-electron oxidation of protoporphyrinogen-IX to protoporphyrin-IX, a critical step in heme biosynthesis 1. The gene is located on chromosome 1 as a single-copy gene containing 13 exons 1. PPOX functions as a mitochondrial inner membrane protein involved in oxygen-dependent porphyrin metabolism [GO annotations]. Loss-of-function mutations in PPOX cause variegate porphyria (VP), an autosomal dominant disorder characterized by decreased enzyme activity 2. VP presents with two distinct phenotypes: photosensitive skin disease with blistering on sun-exposed areas 3, and acute neurovisceral crises involving severe abdominal pain, neurological symptoms, and electrolyte abnormalities like hyponatremia 4. Acute VP attacks are clinically less severe than those of acute intermittent porphyria but require emergency management with intravenous hemin, supportive care, and avoidance of porphyrinogenic triggers 5. Long-term complications include chr1 kidney disease, hepatocellular carcinoma, and hypertension 5. Genetic testing of PPOX confirms diagnosis in biochemically positive patients 6, with over 30 characterized mutations identified globally, many family-specific 7.