Here we report the preliminary results of the first systematic screen for proteins that interact with PAX6. We used sequence alignment algorithms and secondary structure prediction programs to define a new domain of 32 amino acids at the C-terminal end of the PAX6 protein. We then screened a brain library with this peptide using the yeast two-hybrid technique and identified three novel interacting proteins, HOMER3, DNCL1 and TRIM11. The interaction between PAX6 and these proteins was disrupted by naturally occurring C-terminal PAX6 mutations.