The latent transforming growth factor-beta (TGF-beta) binding protein-1 belongs to a family of matrix glycoproteins that is functionally associated with the assembly and secretion of TGF-beta. We have isolated and sequenced a murine approximately 15-kbp contig containing part of Ltbp-1 and used a mouse-hamster radiation hybrid panel to determine its chromosomal localization on distal mouse chromosome 17. This map location is syntenic to human chromosomal subband 2p21-22. Similarly, human LTBP-1 was mapped to 2p21-22 by fluorescence in situ hybridization. Like in humans, the murine Ltbp-1 gene directs the synthesis of two different transcript sizes encoding two alternatively spliced isoforms (Ltbp-1S and Ltbp-1L), which are regulated in a tissue-and stage-dependent manner. Sequence analysis and database searches further reveal that the upstream regions of both isoforms are devoid of TATA and CAAT boxes but contain other putative binding sites for several transcription factors conserved in mouse and human. The utilization of different promoters and their evolutionarily conservation further emphasize the complex regulation of Ltbp-1.