In this study, we demonstrated consistent FCRL5 expression, even in situations where BCMA expression diminished, following the administration of BCMA-directed CAR-T cells, and, based on this finding, engineered FCRL5-specific CAR-T cells adept at recognizing FCRL5 in MM cells and impede tumor growth both in vitro and in murine xenograft models. Here, FCRL5 is linked to neoplasm.