The functional importance of VCP to maintaining cellular protein homeostasis.

The AAA-ATPase (ATPases associated with diverse cellular activities) valosin-containing protein (VCP), is essential for many cellular pathways including but not limited to endoplasmic reticulum-associated degradation (ERAD), DNA damage responses, and cell cycle regulation. VCP primarily identifies ubiquitylated proteins in these pathways and mediates their unfolding and degradation by the 26S proteasome. This review summarizes recent research on VCP that has uncovered surprising new ways that this ATPase is regulated, new aspects of recognition of substrates and novel pathways and substrates that utilize its activity.