KRIT1 and cerebral cavernous malformation: In the present study, we show that human CCM lesions display increased levels of p62/SQSTM1, an autophagic marker that accumulates when autophagy is inhibited, and demonstrate that both KRIT1 and CCM3 loss-of-function impair autophagy through the up-regulation of the mechanistic target of rapamycin (mTOR) pathway, leading to a defective quality control system and the accumulation of aberrant and aggregated proteins.