ZMPSTE24 cleaves the C-terminal 15 amino acids of prelamin A to generate mature lamin A. Mutations in the genes encoding either ZMPSTE24 or prelamin A that block this cleavage step cause premature aging diseases that include Hutchinson-Gilford progeria syndrome, mandibuloacral dysplasia, and restrictive dermopathy, which result from the accumulation of uncleaved farnesylated prelamin A (11, –, 16). This evidence concerns the gene ZMPSTE24 and restrictive dermopathy.