Praziquantel, the anti-schistosomiasis drug, is known to induce the bipolar (2-head) phenotypes in regenerative planarian flatworm Dugesia japonica, yet actual mechanism behind this head-instead-of-tail phenotype remains unclear. Previous studies has shown a specific voltage-gated calcium channel subtype, Cav1B, potentiates the bipolar phenotypes among regenerative planarians induced by praziquantel. Here I identify a new transmembrane protein, macoilin, in planarian that has the identical effects to that of Cav1B by RNAi methods. I have shown that by inhibiting the mRNA of macoilin, the regenerative worm under the exposure of praziquantel has a significant increase of bipolar phenotype penetrance compared to the naïve worms. Experimental data has also shown that the macoilin RNAi worms acquire defects in motility after regeneration. These results indicate a possible protein (macoilin) involved in praziquantel-induced signaling pathway that may bring light to the future studies of the mechanism of praziquantel.