Ependymins represent regeneration-responsive piscine glycoproteins and in many teleost fish they appear as the predominant cerebrospinal fluid constituents. Thus far, no homologous sequences have been characterized unambiguously in mammals. Sialic acid residues of the N-linked carbohydrate moiety of ependymins are responsible for their calcium-binding capacity. Ependymins from some species bear the L2/HNK-1 epitope typical of many cell adhesion molecules. After their synthesis in fibroblast-like cells of the inner endomeningeal layer, soluble ependymins are widely distributed via the cerebrospinal fluid system. Furthermore, ependymins presumably cross the intermediate endomeningeal barrier layer by way of a transcellular transport phenomenon (transcytosis). A bound form of ependymins is associated with collagen fibrils of the extracellular matrix typically found around cerebral blood vessels. Here, they might modulate the endothelial barrier function. Generally, ependymins are thought to represent a new class of possibly antiadhesive extracellular matrix proteins playing a role in specific cell contact phenomena (e.g., during regeneration).