Cellular asymmetry is critical for the development of multicellular organisms. PARD (partitioning-defective) proteins play important roles in asymmetric cell division and polarized growth, whereas Cdc42 and Rac mediate establishment of cell growth and polarity and contribute to oncogenic transformation by Ras. The human PARD6, a 345 amino acid polypeptide, has a PDZ domain and a CRIB-like (Cdc42/Rac interactive binding) motif. PARD6 interacts with GTPbound Rac and Cdc42 via this motif and with the atypical PKC isoforms PKCi/l and PKCz via N-terminal head to head association. These interactions allow formation of a ternary complex in vitro and in vivo, which is implicated in the formation of normal tight junctions at epithelial cell-cell contacts and is also involved in the polarization of mother cells before asymmetric cell division in C. elegans. PARD6 acts through PARD3 by localizing or maintaining the PARD3 protein at the cell periphery. PARD6A, also designated PAR-6a, PAR6C, TAX40 and TIP-40, is expressed in pancreas, skeletal muscle, brain and heart, and is weakly expressed in kidney and placenta. PAR6B is expressed in pancreas and in both adult and fetal kidney, and is weakly expressed in placenta and lung.