VCPIP1 is a deubiquitinating enzyme that plays crucial roles in cellular homeostasis, immune regulation, and pathogen responses. The protein functions primarily through its deubiquitinase activity to stabilize target proteins by removing polyubiquitin chains, though it can also act through non-catalytic mechanisms 1. VCPIP1 forms functional complexes with VCP/p97 to regulate post-mitotic Golgi reassembly, where it sits over the VCP hexamer's C-terminal exit tunnel in an unusual C3 to C6 symmetric architecture 23. In immune regulation, VCPIP1 acts as a positive regulator of TLR4 signaling by maintaining IRAK1/2 protein stability through non-catalytic reduction of their K48-linked ubiquitination 1, while also negatively regulating NF-κB pathways by deubiquitinating and stabilizing the inhibitory protein Erbin 4. The enzyme demonstrates neuroprotective functions by promoting microglial autophagy through inhibition of the PI3K/AKT/mTOR pathway, thereby ameliorating sepsis-associated encephalopathy 5. VCPIP1 also facilitates cancer progression in pancreatic adenocarcinoma by deubiquitinating YAP, creating a positive feedback loop that enhances Hippo/YAP signaling 6. Additionally, VCPIP1 serves as a multi-functional positive regulator of hepatitis B virus by stabilizing HBx protein and directly modulating viral promoter/enhancer activities 7.