Notably, activation of the BRD4/PDLIM4/p21 pathway enhanced chemosensitivity to doxorubicin in both LUAD cells and xenograft tumor models.<h4>Conclusions</h4>Given the high mutation frequency of PDLIM4 recorded in the TCGA cancer database, our findings reveal a critical regulatory signaling pathway that suppresses LUAD progression and augments chemotherapy efficacy. The gene discussed is BRD4; the disease is neoplasm.