Overlapping cDNA clones from human heart and melanoma libraries were used to establish the 1587-residue sequence of a novel protein (LTBP-4) belonging to the family of extracellular microfibrillar proteins which also bind transforming growth factor-β. LTBP-4 consists of 20 EG modules, 17 of them with a consensus sequence for calcium binding, 4 TB modules with 8 cysteines and several proline-rich regions. Northern blots demonstrated a single 5 kb mRNA which is highly expressed in heart but also present in skeletal muscle, pancreas, placenta and lung. The modular structure predicts that LTBP-4 should be a microfibrillar protein which probably also binds TGF-β.