Medin amyloid is found in the medial layer of the aorta in almost 100% of the Caucasian population over 50 years of age. The medin fragment is 5.5 kDa and derives from the C2-like domain of the precursor protein lactadherin. We have previously reported immunohistochemical findings showing that medin amyloid co-localizes with elastic fibers of arteries and herein we show that lactadherin also is associated with elastic structures of human aortic material. In addition, results from in vitro binding assays demonstrate that both medin and lactadherin bind to tropoelastin in a concentration-dependent fashion, suggesting that the lactadherin-tropoelastin interaction is mediated via the medin domain. It is possible that lactadherin, which is a cell adhesion protein, in this way connects smooth muscle cells to the elastic fibers of arteries. Given that both medin and lactadherin interact with elastic fibers, elastin is probably an important component in the formation of medin amyloid.