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The widely expressed SP100 and the leukocyte-specific proteins SP110 and SP140 have been associated with transcriptional regulation and various human diseases. Here, we have characterized the SP100 family member SP140L. The genome sequence analysis showed the formation of<jats:italic>SP140L<\/jats:italic>gene through rearrangements of the two neighboring genes,<jats:italic>SP100<\/jats:italic>and<jats:italic>SP140<\/jats:italic>, during the evolution of higher primates. The<jats:italic>SP140L<\/jats:italic>expression is interferon-inducible with high transcript levels in B cells and other peripheral blood mononuclear cells. Subcellularly, SP140L colocalizes with SP100 and SP140 in nuclear structures that are devoid of SP110, PML, or p300 proteins. Similarly to SP100 and SP140 protein, we detected serum autoantibodies to SP140L in patients with primary biliary cirrhosis using luciferase immunoprecipitation system and immunoblotting assays. 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