While the functions of TTC12 and ANKK1 are not well established, present knowledge suggests that they may be related in part to the development or modulation of dopaminergic neurotransmission. TTC12 encodes a protein called TPARM, which includes one tetratricopeptide repeat domain (TPR) and three armadillo repeat domains (ARMs) (Katoh and Katoh, 2003). Its ARM, included in a family of proteins containing several 42-amino acid repeat domains, is thought to play a variety of roles at the cellular level, including regulation of desmosome assembly, cell adhesion, neurogenesis, signal transduction, and post developmental synaptogenesis. β-catenin, a prototypical ARM-containing protein, was recently identified as a risk locus for bipolar affective disorder (Baum et al., 2007). These findings, and others, suggest that the ARMs encoded by TTC12 might also be involved in the cascade of events in the Wnt signal transduction pathway that occurs in early neuronal development (Castelo-Branco and Arenas, 2006; Castelo-Branco et al., 2004), and could potentially influence the level of dopamine D2 receptors and thereby modulate SD risk.
