UBXN2B (UBX domain protein 2B) is an adapter protein that functions primarily in organellar biogenesis and cell division. It serves as a cofactor for the AAA+-ATPase VCP/p97, regulating its nucleocytoplasmic shuttling to coordinate cytosolic and nuclear functions 1. In the cytoplasm, UBXN2B-VCP complexes mediate Golgi and endoplasmic reticulum biogenesis, maintenance, and reassembly during mitosis 2. During mitotic progression, UBXN2B regulates spindle orientation by limiting cortical NuMA recruitment through PP1/Repo-Man phosphatase signaling, independent of Aurora A kinase 3. Nuclear UBXN2B-VCP complexes are critical for DNA damage repair; disease-associated VCP mutations show enhanced p37 binding and reduced nuclear VCP localization, increasing DNA damage susceptibility 1. UBXN2B associates with FAM104 proteins and other VCP cofactors to promote nuclear p97 import 4. Disease relevance includes multiple sclerosis, where UBXN2B shows sex-differential dysregulation in brain tissue 5, metabolic liver disease where the UBXN2B/CYP7A1 locus interacts with BMI 6, uveal melanoma where UBXN2B contributes to metastatic risk 7, and narcolepsy where UBXN2B variants associate with symptom onset age 8.