UROS (uroporphyrinogen III synthase) catalyzes the cyclization of hydroxymethylbilane to uroporphyrinogen III, a critical branch point in heme biosynthesis 1. As the fourth enzyme in the heme biosynthetic pathway, UROS enables production of porphyrins that serve as essential cofactors for diverse cellular processes, including oxygen transport (heme) and methionine synthesis (vitamin B12) 1. UROS is localized to chromosome 10.2-q26.3 2. Congenital erythropoietic porphyria (CEP) results from biallelic UROS mutations causing deficient enzymatic activity 3. This autosomal recessive disorder leads to pathologic accumulation of Type I porphyrins, particularly the photoreactive uroporphyrinogen I and coproporphyrinogen I, which damage erythrocytes 4. Clinical manifestations range from severe (non-immune hydrops fetalis in utero) to mild (adult-onset dermatologic disease) depending on residual UROS activity 3. Patients exhibit exquisite photosensitivity causing bullous lesions, erythrodontia, corneal scarring, and hemolytic anemia 4. Management includes strict light avoidance and, in severe transfusion-dependent cases, hematopoietic stem cell transplantation offers curative potential 4. Emerging therapeutic approaches include chaperone-mediated UROS rescue, gene therapy, and proteasome inhibition 3.