Deubiquitinating protein VCPIP1

VCPIP1 is a deubiquitinating enzyme that catalyzes hydrolysis of Lys-11- and Lys-48-linked polyubiquitin chains (UniProt: Q96JH7). It functions in DNA repair by promoting deubiquitination of SPRTN to facilitate removal of DNA-protein cross-links following ATM or ATR phosphorylation. VCPIP1 also plays roles in post-mitotic reassembly of the Golgi apparatus and endoplasmic reticulum through VCP-mediated mechanisms (UniProt: Q96JH7).

In Alzheimer's Disease, VCPIP1 is downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The protein showed a mean log2 fold-change of −0.37 across measured subcellular fractions in TMT-labeled quantitative proteomics. This reduction may impact DNA repair capacity and organellar homeostasis in AD neurons, processes relevant to neurodegeneration and proteostasis maintenance.