Thus, in the study presented, we set out to unravel the role of INPP4B in RB chemoresistance by analyzing INPP4B expression in etoposide resistant RB cell lines and chemotherapy-treated RB patient tumors and investigating the effect of lentiviral INPP4B overexpression on etoposide-resistant RB cell viability, proliferation, apoptosis, anchorage-independent growth, and tumor formation in vitro and in vivo. Here, INPP4B is linked to neoplasm.