Contactin-6, is a 130kD member of the TAG/F3 subgroup of Contactin GPI-linked neuronal adhesion proteins (1,2). Mature mouse Contactin-6 consists of six immunoglobulin-like domains, a flexible linker region, four fibronectin type III domains, and a GPI anchor (3-5). Mouse Contactin-6 shares 90-96aa sequence identity with human and rat Contactin-6, respectively. Alternate splicing generates an isoform with a 17aa deletion in the first Ig-like domain (3). Contactin-6 expression is upregulated postnatally in the cerebellum, brainstem, and hippocampus, and it shows differential expression within various structures of the brain (3,5-7). In the cerebellum, it is presynaptically localized at synapses between excitatory glutamatergic parallel fibers and Purkinje cells (7). Contactin-6 associates in cis with CHL-1 and in trans with Notch-1 on oligodendrocytes (6,8). Its binding to Notch-1 triggers translocation of the Notch intracellular domain to the nucleus and promotes oligodendrogenesis (6). Contactin-6 function is important in the postnatal development and function of the cerebellum, as shown in knockout mice which exhibit poor motor coordination (5,7).