RELA and neoplasm: Our work reveals that SPTBN1 functions to control the stability of the p65 subunit of the NF-κB superfamily through collaboration of the suppressor of cytokine signaling 1 (SOCS1) protein, an E3 ligase of p65, and that this novel regulatory cascade might be an important molecular mechanism underlying the loss of tumor suppressive function of SPTBN1 during cancer development and progression.