In conclusion, this study revealed that pharmacological modulation of P2X4R by ivermectin or 5‐BDBD does not affect the development of ARPKD in PCK rats, which may provide insights for future studies on investigating the therapeutic potential of adenosine triphosphate (ATP)‐P2 signaling in PKD diseases. The gene discussed is P2RX4; the disease is autosomal recessive polycystic kidney disease.