Although TSC-associated angiomyolipomata exhibit a ‘second hit’ at the involved TSC locus [22] with loss of protein expression [23], the mechanism for TSC cystic disease is nuanced, given that the majority of renal cysts in a mouse model maintain their Tsc locus integrity [24,25] and human TSC cysts continue to express both tuberin and hamartin [26]. This evidence concerns the gene TSC1 and cystic kidney disease.