UBXN1 (UBX domain protein 1) is a multifunctional ubiquitin-binding protein that serves as a VCP/p97 cofactor regulating diverse cellular processes. Structurally, UBXN1 contains UBA and UBX domains enabling binding to ubiquitinated substrates and the VCP-NPL4-UFD1 AAA-ATPase complex 1. Primary function centers on immune homeostasis and protein quality control. UBXN1 negatively regulates innate immunity by disrupting RIG-I-like receptor and NF-κB signaling pathways. It inhibits the MAVS/TRAF3/TRAF6 signalosome, preventing excessive RLR activation following viral infection. Additionally, UBXN1 suppresses TNFα-triggered NF-κB signaling through interactions with cIAPs and CUL1, thereby stabilizing NF-κB inhibitor IκBα. In mitochondrial homeostasis, UBXN1 coordinates with VCP to facilitate PINK1/PRKN-dependent mitophagy by promoting MFN2 removal from the outer mitochondrial membrane 1. UBXN1 also interacts with prohibitin to maintain mitochondrial integrity 2. Disease relevance is substantial: UBXN1 expression is upregulated in hepatocellular carcinoma and colorectal cancer, promoting tumor progression 23. Conversely, UBXN1 depletion enhances apoptosis resistance under hypoxia 4. In gastric cancer, METTL16-mediated m6A methylation regulates UBXN1 expression, linking epigenetic mechanisms to tumorigenesis 5. Clinically, UBXN1 represents a potential therapeutic target for cancers with elevated expression and a candidate marker for patient prognosis.