Uroporphyrinogen-III synthase (HemD) catalyzes the asymmetrical cyclization of tetrapyrrole (linear) to uroporphyrinogen-III, the fourth step in the biosynthesis of heme. This ubiquitous enzyme is present in eukaryotes, bacteria and archaea. Mutations in the human uroporphyrinogen-III synthase gene cause congenital erythropoietic porphyria, a recessive inborn error of metabolism also known as Gunther disease.