Protocadherins comprise the largest group within the cadherin family of calcium-dependent cell-cell adhesion molecules. Protocadherin 18 (PCDH18) was initially identified through screening of human and mouse ESTs using conserved cytoplasmic domain motifs. Tissue screening revealed PCDH18 broad expression in tissues such as brain, liver, heart, kidney, lung, and trachea. PCDH18 expression is also temporally and spatially regulated in the mouse embryonic brain and interacts with Disabled-1, an intracellular adapter protein involved in neuronal migration and cell positioning during mammalian brain development. PCDH18 was also found to be expressed in the developing zebrafish neural tube and central nervous system, lending support to the hypothesis that PCDH18 may play a role during brain development.