[7] Recent work, using the mouse (Mus musculus) and zebrafish (Danio rerio) as model organisms, identified an ancient role of BCL9 and BCL9L as key factors required for cardiac development.

[8] This work emphasises the tissue-specific nature of the Wnt/β-catenin mechanism of action, and implicates alterations in BCL9 and BCL9L in human congenital heart defects.

BCL9 and BCL9L have been shown to take part in other tissue-specific molecular mechanisms, showing that their role in the Wnt signaling cascade is only one aspect of their mode of action.

[12] BCL9, together with the paralogue protein BCL9l and PYGO2 also have cytoplasmic functions during tooth development and is particularly important for the formation of enamel.

Bcl9, Bcl9l, and Pygo2 are present in the cytoplasm of ameloblasts, the cells that secrete enamel proteins, and colocalize in these cells with amelogenin, the main component of enamel, encoded by the AMELX gene, which has been already implicated as a causative factor of Amelogenesis Imperfecta in humans.