Proposed mechanism for the role of ALAS2 as a modifier gene in CEP. An enhanced kinetic property of the mutated ALAS2 enzyme would cause an increased production of the linear tetrapyrrole HMB, the substrate of UROS. The increased supply of HMB associated with a defective UROS enzyme would lead to the aggravated CEP phenotype. (A) normal individual; (B) CEP patient wild-type for ALAS2; and (C) CEP patient with ALAS2 mutation.