BBOX1

BBOX1 (gamma-butyrobetaine hydroxylase 1), also known as γ-BBH, is a key enzyme catalyzing the final step of L-carnitine biosynthesis. It is highly expressed in the kidney and demonstrates tissue-specific roles in different cancers. In triple-negative breast cancer (TNBC), BBOX1 exhibits oncogenic function by binding to and stabilizing the IP3R3 calcium channel, thereby promoting calcium-dependent mTORC1 signaling and glycolysis to support tumor growth .
Conversely, in clear cell renal cell carcinoma (ccRCC), BBOX1 acts as a tumor suppressor. Its expression is frequently lost, and restoration disrupts the DCLK2-TBK1 interaction, inhibiting the downstream oncogenic TBK1-mTORC1 signaling axis and glycolysis. The known inhibitor mildronate targets BBOX1, highlighting its potential as a therapeutic target, though its divergent roles necessitate context-dependent drug development strategies .