Transitional endoplasmic reticulum ATPase (VCP) binds to the C-terminal region of Dorfin (an ubiquitin ligase) and its ATPase activity contributes to the E3 activity of Dorfin. It helps glycoprotein 78 (Gp78) in coupling ubiquitination to degradation of 3-hydroxy-3-methylglutaryl coenzyme A reductase and has an important role in the recognition and degradation of endoplasmic reticulum-associated degradation (ERAD) substrates. VCP also aids ring finger protein 8 (RNF8) to mediate assembly of signaling complexes. Missense mutations in the VCP gene leads to inclusion body myopathy associated with Pagetμs disease of bone and front temporal dementia. It is characterized by the presence of vacuoles in the cytoplasm of muscle fibers.
