We identified a novel alternative splicing event that constitutively produces a truncated active form of human sterol regulatory element-binding protein 1 (SREBP-1). A cDNA of this splicing variant (named SREBP-1 Delta) contains a translational stop codon-encoding exon sequence between exons 7 and 8. It produces SREBP-1a Delta (470 a.a.) and SREBP-1c Delta (446 a.a.) proteins that lack transmembrane and C-terminal regulatory sequences necessary for localization of SREBP-1 to the endoplasmic reticulum. A luciferase reporter assay showed that SREBP-1a Delta and SREBP-1c Delta transactivated lipogenic gene promoters to the same extent as that induced by N-terminal active fragments of SREBP-1a and SREBP-1c, respectively. SREBP-1 Delta mRNA is expressed in human cell lines as well as adipose and liver tissues. Expression levels ranged from 5% to 16% of total SREBP-1 expression. The ratio of SREBP-1 Delta expression to total SREBP-1 expression in HepG2 cells was not affected by either insulin or high glucose treatment. (c) 2008 Elsevier Inc. All rights reserved.