The TSC1/TSC2 complex, through its GTPase-activating protein activity towards the small G-protein Rheb, is a critical negative regulator of mTOR complex 1 (mTORC1).32 Inactivating mutations of TSC1/TSC2 result in mTOR pathway activation and these alterations have been shown, collectively, to confer sensitivity to mTOR inhibitors in patients with hamartomatous syndromes, such as tuberous sclerosis complex.33–35 These findings may explain the response to E/P seen in our mUC patients harbouring inactivating mutations in TSC1/TSC2 or activating mutations in mTOR.14 The gene discussed is TSC1; the disease is tuberous sclerosis.