BTRC is an E3 ubiquitin ligase adaptor that functions as the substrate recognition component of SCF ubiquitin-protein ligase complexes, mediating ubiquitination and proteasomal degradation of phosphorylated target proteins. BTRC recognizes and binds phosphorylated substrates, targeting them for degradation through K48-linked ubiquitination. Its major substrates include negative regulators of key signaling pathways: NFKBIA/NFKBIB/NFKBIE, which upon degradation liberate NFKB for nuclear translocation; CTNNB1/β-catenin in Wnt signaling; cell cycle regulators (CDC25A, CDK4); circadian clock components (PER1, PER2); and metabolic regulators (DEPTOR, TFE3, MITF in mTORC1 signaling). Recent evidence indicates BTRC also mediates degradation of ATGL in hepatic steatosis and PDCD4 in hepatocellular carcinoma progression 12. Disease associations span metabolic disorders, cancer, and developmental abnormalities; elevated BTRC correlates with poor prognosis in glioblastoma and colorectal cancer 34. A BTRC microduplication of 120 kb has been associated with split hand/foot malformation type 3 in a Chinese family 5, indicating that dosage imbalance disrupts normal limb development. Therapeutically, BTRC inhibition via MEK inhibitors (e.g., trametinib) restores mitophagy in breast cancer metastasis 6, and selective HDAC7 inhibitors like pinocembrin enhance immunotherapy by modulating BTRC-mediated SRSF7 degradation in bladder cancer 7.