Collagen XV, a multifaceted multiplexin present across tissues and species

Type XV collagen is a non-fibrillar collagen that is associated with basement membranes and belongs to the multiplexin subset of the collagen superfamily. Collagen XV was initially studied because of its sequence homology with collagen XVIII/endostatin whose anti-angiogenic and anti-tumorigenic properties were subjects of wide interest in the past years. But during the last fifteen years, collagen XV has gained growing attention with increasing number of studies that have attributed new functions to this widely distributed collagen/proteoglycan hybrid molecule. Despite the cumulative evidence of its functional pleiotropy and its evolutionary conserved function, no review compiling the current state of the art about collagen XV is currently available. Here, we thus provide the first comprehensive view of the knowledge gathered so far on the molecular structure, tissue distribution and functions of collagen XV in development, tissue homeostasis and disease with an evolutionary perspective. We hope that our review will open new roads for promising research on collagen XV in the coming years. •Type XV collagen belongs to the multiplexin subset of the collagen superfamily.•It is evolutionarily conserved collagen and associated with basement membranes.•This collagen/proteoglycan hybrid molecule contains an anti-angiogenic restin domain.•It has important functions in the cardiovascular and the neuromuscular systems.•Its expression is dysregulated in various diseases including cancers.