UBN2 (ubinuclein 2) is a chr7-associated protein that functions as a core component of the HIRA histone chaperone complex, playing critical roles in chr7 organization and nucleosome assembly. UBN2 associates with HIRA through an evolutionarily conserved Hpc2-related domain that directly interacts with HIRA's N-terminal WD repeats 1. In ALT cancer cells, the HIRA-UBN1/UBN2 complex deposits histone H3.3 at telomeres to maintain chr7 accessibility and prevent detrimental R-loop accumulation and transcription-replication conflicts, supporting ALT pathway activation 2. UBN2 expression is aberrantly elevated across multiple cancer types. In acute myeloid leukemia, UBN2 mediates PPARα signaling downstream of miR-455-3p to promote apoptosis and autophagy 3. In non-small-cell lung cancer, elevated UBN2 expression (regulated by the circ_0060967/miR-660-3p axis) promotes cell proliferation, migration, and invasion 4. In prostate cancer, UBN2 functions downstream of ADAM9 to promote castration resistance through AKR1C3 induction 5. In colorectal cancer and ATLL lymphoma, miR-802 and miR-575 respectively suppress UBN2 to inhibit tumorigenesis [PMID:33177873; 63]. Additionally, de novo UBN2 mutations have been identified in autism spectrum disorder with abnormal head circumference 7, suggesting roles in neurodevelopmental processes beyond cancer biology.