LMNA and progeroid syndrome: The targeting of HP1 isoforms for proteasomal degradation in these cells thus provides an additional mechanism through which lamin mutants can alter chromatin organization that is distinct from the toxicity of LAΔ50 or overexpressed pre-lamin A. A recent study has identified another progeria mutation, E145K that is highly disruptive of nuclear structure but does not respond to treatment with a farnesyl transferase inhibitor [46].