Collagens type XV and XVIII are closely related non-fibrillar collagens that define the multiplexin (multiple triple helix domains with interruptions) subfamily of collagens. Both are homotrimers characterized by highly interrupted collagenous domains flanked by large globular domains with attached glycosaminoglycan chains. Collagen XV is localized in the outermost layer of the basement membrane (BM) and in the fibrillar matrix. Collagen type XV is the only collagen able to self-assemble into higher-order cruciform structures with intermolecular binding sites (Myers et al. 2007). The interaction is mediated by interactions between triple helical regions (Hurskainen et al. 2010). It is predominantly located in the basement membranes of microvessels, and cardiac and skeletal myocytes (Hägg et al. 1997), where it binds basement membrane and microfibrillar components such as fibulin-2, nidogen-2, vitronectin, laminin, and fibronectin (Sasaki et al. 2000, Hurskainen et al. 2010). It may form a bridge between fibrillar collagens and the basement membrane (Amenta et al. 2005), acting as a molecular shock absorber to stabilize and enhance resilience to compressive and expansive forces (Myers et al. 2007). Lack of Collagen type XV in Col15a1-null mice resulted in increased permeability and impaired microvascular hemodynamics, distinct early-onset and age-dependent defects in heart structure and function, a poorly organized fibrillar collagen matrix with marked interstitial deposition of nonfibrillar protein aggregates, increased tissue stiffness, and irregularly organized cardiomyocytes (Rasi et al. 2010a). Col15a1 knockout also leads to loosely packed axons in C-fibers and polyaxonal myelination. Simultaneous knockout with laminin alpha-4 leads to severely impaired radial sorting and myelination (Rasi et al. 2010b).

The C-terminal non-collagenous region of collagen type XV is known as restin because it resembles endostatin, having antiangiogenic effects (Ramchandran et al. 1999, Sasaki et al. 2000).