Zinc metalloprotease ZMPSTE24 (ZMPSTE24)

ZMPSTE24 is a zinc-dependent transmembrane metalloprotease that plays a critical role in the post-translational processing of prelamin A, an essential step for the maturation of lamin A, a key structural component of the nuclear lamina. It catalyzes two sequential proteolytic cleavages on prelamin A: first, removing the C-terminal “aaX” tripeptide after farnesylation, and second, cleaving off an additional 15 amino acids upstream. This activity is essential for normal nuclear architecture and function. Mutations in ZMPSTE24 cause defective processing of prelamin A, leading to several severe disorders, including Hutchinson-Gilford Progeria Syndrome, mandibuloacral dysplasia, and restrictive dermopathy. It also plays a role in protein quality control, membrane stress response, and antiviral defense.

Other names

CAAX prenyl protease 1 homologFACE1

Proteolytic cleavage of prelamin A at the CAAX motif and upstream sequences.