One important function of the neurofibromatosis type 1 (NF1) product neurofibromin is the negative regulation of Ras activity on the cell membrane. Here, we describe an alternative splice product of the N-terminus of the NF1 gene. In this splice product, termed NF1-10a-2, the 45 bp exon 10a-2 is inserted between exons 10a and 10b. Amino acid sequence analysis for motifs showed that the new splice product contains a transmembrane segment not found in wild-type neurofibromin. The overall expression was found to be very low in comparison to the expression of the wild-type mRNA in all human primary and tumor cells examined. Because transcripts were found in the majority of human tissues examined, we assume a housekeeping function of this splice product. Investigation of the intracellular localization of an NF1-10a-2-EGFP fusion protein in HeLa cells revealed a preferential localization in perinuclear granular structures. We therefore assume that NF1-10a-2 has a function on an intracellular membrane. (C) 2002 Elsevier Science (USA). All rights reserved.