VCP (Valosin-Containing Protein) is a highly conserved AAA+ ATPase involved in a wide range of cellular functions, including protein quality control, endoplasmic reticulum-associated degradation (ERAD), autophagy, mitochondrial function regulation, cell cycle control, DNA damage response, and the formation and clearance of stress granules. By interacting with various cofactors, VCP recognizes ubiquitinated proteins and assists in their unfolding and degradation, thereby maintaining cellular protein homeostasis. In the nervous system, VCP plays a critical role in neurodegenerative diseases, where its mutations can lead to protein aggregation and organelle dysfunction, contributing to neuronal pathology. Additionally, VCP is implicated in cardiovascular diseases, with its dysfunction associated with myocardial ischemia/reperfusion injury, cardiac hypertrophy, and heart failure. Given its involvement in multiple diseases, VCP has emerged as a potential therapeutic target, particularly for neurodegenerative and cardiovascular conditions.
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