TSC2 and lymphangioleiomyomatosis: LAM is associated with TSC2 mutations [31] resulting in activation of the mechanistic target of rapamycin complex 1 (mTORC1) [32], A seminal clinical trial showed that the mTORC1 inhibitor sirolimus stabilizes lung function and improves symptoms in LAM patients while drug exposure continues [33], but long-term benefit and toxicity are unknown, and some patients do not respond.