VCP (valosin containing protein) is an essential AAA-ATPase that functions as a central regulator of protein homeostasis and cellular quality control mechanisms. VCP plays critical roles in endoplasmic reticulum-associated degradation (ERAD), where it forms complexes with UFD1 and NPLOC4 to extract misfolded proteins for proteasomal degradation 1. The protein is essential for autophagy initiation and maturation, with UFMylation on K109 stabilizing BECN1 and facilitating PtdIns3K complex assembly 1. VCP also promotes autophagy progression by recruiting USP2 to stabilize FASN through deubiquitination 2. Beyond protein degradation, VCP is involved in Golgi fragmentation during mitosis and nuclear envelope reformation. Disease-associated mutations in VCP cause neurodegenerative disorders including Charcot-Marie-Tooth disease, frontotemporal dementia, and amyotrophic lateral sclerosis, with mutant microglia displaying immune and lysosomal dysfunction 3. In cancer, VCP acts as an oncogene, promoting hepatocellular carcinoma progression through PI3K/AKT/mTOR pathway activation via HMGB1 stabilization 4 and facilitating triple-negative breast cancer through the VCP-TMEM63A-DERL1 signaling axis 5. VCP inhibitors like CB-5083 and CB-5339 have entered clinical trials as promising cancer therapeutics 67.