Transcriptional modification by alternative splicing is known to be involved in the regulation of programmed cell death. Recently, alternative splice variants of the TNF-related apoptosis inducing ligand (TRAIL/APO2L) and of the death receptor TRAIL-R2/DR5 have been identified. In this study, we report the identification of a novel alternative splice variant of the decoy receptor with a truncated death domain TRAIL-R4 lacking exon 3, which we designated TRAIL-R4-beta. As revealed by BLAST search we identified the genomic organisation of the TRAIL-R4 gene which consists of 9 exons. Loss of exon 3 resulted in the truncation of the first complete cysteine rich domain 1 which is known to be involved in ligand-receptor-complex. In conclusion, alternative splicing might be involved in functional fine-tuning of TRAIL-induced programmed cell death. (c) 2006 Elsevier Inc. All rights reserved.