Polycomb group (PcG) proteins are required for maintaining the repressed state of developmentally important genes such as homeotic genes. Polycomblike (Pcl), a member of PcG genes with two characteristic PHD finger motifs, was shown to strongly enhance the effects of PcG genes in Drosophila. Three Pcl genes exist in the mouse genome, with their function largely unknown. Our previous studies demonstrate that the chick Pcl2 is essential for the left–right asymmetry by silencing Shh expression in the right side of the node (Wang et al., [2004b] Development 131:4381–4391). To elucidate the in vivo role of mouse Pcl2, we generated Pcl2 mutant mice. Phenotypic analyses indicate the normal development of left–right asymmetry in the Pcl2 mutant mice. However, Pcl2 mutant mice exhibit posterior transformation of axial skeletons and other phenotypic defects, with a relatively low penetrance. These results demonstrate that Pcl2 is dispensable for the normal left–right axis development in mice. Developmental Dynamics 236:853–861, 2007. © 2007 Wiley-Liss, Inc.