FREM2 is a 3,169 amino acid single-pass type I membrane protein that localizes to the extracellular side of the cell membrane and contains five Calx-beta domains, as well as 12 CSPG repeats. Functioning as an extracellular matrix protein, FREM2 is required for the maintenance of skin and renal epithelia and is also thought to be involved in epidermal adhesion events. Defects or mutations in the gene encoding FREM2, which maps to human chromsome 13, are associated with Fraser syndrome, a multisystem malformation that is characterized by ear abnormalities, congenital heart defects and cutaneous syndactyly. FREM2 exists as multiple alternatively spliced isoforms.