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Our studies reveal a novel role of UBR5 in B cell maturation by stabilization of spliceosome components during B cell development and suggests UBR5 mutations play a role in mantle cell lymphoma transformation. Copyright © 2020 American Society of Hematology.Linear ubiquitin chain assembly complex (LUBAC) is a key regulator of NF-kB signaling. Activating single-nucleotide polymorphisms of HOIP, the catalytic subunit of LUBAC, are enriched in patients with activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL),