L1 cell adhesion molecular is a type Ⅰ membrane glycoprotein of immunoglobulin superfamily. L1 is expressed mainly in nervous system and plays important roles in nervous system development, learning and memory. L1 cytoplasmic domain (L1CD) is important for L1 function by mediating signaling. To investigate the molecular mechanisms of signaling mediated by L1CD, yeast two-hybrid assay was carried out to screen the human brain cDNA library using L1CD as the bait. After sequence analysis and BLAST, several candidates were identified. One candidate is PAX6 transcription factor. L1CD and PAX6 cDNA were cloned in expression vectors and cotransfected into COS-7 cells. The interaction between L1CD and PAX6 was verified by co-immunoprecipitation assay. These preliminary results suggest that L1CD may be involved in transcription regulation.