This study identifies a novel oncogenic role and a previously unrecognized phosphorylation substrate of BCKDK in RCC, wherein it promotes tumor progression and drug resistance through AKT phosphorylation at both Thr308 and Ser473 sites and activation of AKT/mTOR and AKT/ABCB1 signaling pathways, offering a promising prognostic marker and therapeutic target for RCC. This evidence concerns the gene ABCB1 and renal cell carcinoma.