Historically, collagens have been defined as extracellular matrix structural proteins whose sequence is characterized by many repeats of a three amino acid unit, GLY-X-Y. However, the latter motif has been identified in certain domains of a number of other proteins including the C1q subunit of complement, the collectins, the asymmetric form of acetylcholinesterase, ficolin and the macrophage scavenger receptors. We describe these molecules and discuss both their structure and their putative functions. Intriguingly, these proteins show similarity to a 180 kD protein component of an epithelial cell/matrix anchorage device called the hemidesmosome. The latter protein is now considered a bona fide member of the collagen superfamily and has been termed type XVII collagen, despite the fact that it is a non-secreted transmembrane protein. We review recent studies on type XVII collagen which provide clues to its potential protein-protein interactions as well as its role in the pathogenesis of two human skin diseases.