In order to elucidate the molecular mechanism of how INPP4B safeguards genome integrity in lung cancer A549 cells, we knocked out INPP4B in these cells by employing Crispr-Cas9 gene editing and discovered an unexpected role of INPP4B in DNA repair by maintaining the stability of Rab50, a critical component of Mre11/Rad50/Nbs1 complex for sensing and tethering DNA double strand breaks in mammalian cells. Here, INPP4B is linked to lung carcinoma.