Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene is 
responsible for the development of renal carcinomas, pheochromocytomas and 
tumours in other organs. The gene product (pVHL) is a central component in the 
oxygen-sensing pathway through its role in the regulation of the 
hypoxia-inducible factor (HIF). Loss of pVHL leads to activation of the HIF 
pathway in normoxia with the concomitant increase in tumour vascularisation due 
to the up-regulation of pro-angiogenic genes. However, although the role of pVHL 
in the regulation of HIF has proved to be important for tumour growth, other 
pVHL functions independent of HIF have been reported and help to explain why 
loss of VHL leads to renal cancer. Studies aimed to characterise other molecular 
pathways that shed light on its physiological roles as a gatekeeper gene in 
kidney and other organs will be very helpful for the development of novel 
anticancer therapies.