We propose that caveolin-1 may serve as a ‘gatekeeper’ for activation of the hypoxia-inducible factor (HIF) pathway a downstream effector molecule of mTOR that accumulates in RCC in response to the loss of function of VHL and promotes angiogenesis, vascular invasion and chemoresistance (Patel et al, 2006). Here, VHL is linked to renal cell carcinoma.