The EMILINs are a new family of glycoproteins of the extracellular matrix. The prototype of this family is the chicken EMILIN that was originally identified in extracts of aortas; it was then found to be widely distributed in several tissues associated with elastin and localized at the interface between amorphous elastin and microfibrils. Based on peptide sequences, chicken and human cDNAs coding for EMILIN were isolated by RT/PCR by screening kidney and heart cDNA libraries. By using a C-terminal fragment of human EMILIN-1 as a bait in the yeast two-hybrid system, a second family member, EMILIN-2, has also been isolated. EMILINs are characterized by a C-terminal gC1q globular domain, a short collagenous sequence, a long coiled-coil region and a new cysteine-rich N-terminal domain that can be considered a hallmark of the family being present also in multimerin. The gene for EMILIN-1 was mapped on chromosome 2p23 overlapping with the promoter region of the ketohexokinase gene. The gC1q domain of EMILIN-1 can form relatively stable and compact homotrimers and this association is then followed by a multimeric assembly of disulfide-bonded protomers. Recombinant EMILIN-1 purified from the supernatant of 293 cells represents a very efficient ligand for cell adhesion of several cell types.