The nuclear lamina is a meshwork of intermediate filaments that lie beneath the inner nucleus membrane, and functions to provide structural scaffolding for the cell nucleus. It also plays a role in chromatin organization, transcription, and mitosis. The main protein constituents of the nuclear lamina are the lamin proteins, principally Lamins A, C, B1, and B2. The ZMPSTE24 is a zinc metalloproteinase that plays a key role in the post-translational processing of the Lamin A protein. Specifically, this enzyme catalyzes a two-step post-translational endo-proteolytic cleavage of the carboxy terminal residues of farnesylated prelamin A to form mature lamin A.
Mutations in the ZMPSTE24 gene have been implicated in two related disorders; Restrictive Dermopathy, and Mandibuloacral Dysplasia (MAD). Both of these are progeroid disorders, the former a lethal disorder characterized by taut skin in utero leading to fetal akinesia and deformation. MAD is characterized by skeletal abnormalities, such as mandibular and clavicular hypoplasia and acroosteolysis.