Most aniridia patients are heterozygous for mutations that introduce a premature termination codon into the PAX6 open reading frame [2,52]. These alleles would be expected to encode truncated proteins or no protein at all if the mutant RNA is degraded by nonsense-mediated decay [52]. We propose that the brain anomalies that have been observed in aniridia patients may be partly explained by impaired interaction between PAX6 and HOMER3, DNCL1 and TRIM11. The neurobehavioural phenotype associated with 1615del10 and the polymicrogyria associated with X423L may result from a specific effect of these unusual C-terminal extension mutations. There is evidence that signalling and transport mechanisms that were initially characterized in the brain may also be conserved in the retina, suggesting that impaired PAX6 protein-protein interactions may also have implications for the retinal defects observed in individuals with PAX6 mutations [53,54].