The tuberous sclerosis complex (TSC) 1 and 2 proteins associate with TBC1D7 to form the TSC complex, which is an essential suppressor of mTOR complex 1 (mTORC1), a ubiquitous driver of cell and tissue growth. Loss-of-function mutations in TSC1 or TSC2, but not TBC1D7, give rise to TSC, a pleiotropic disorder with aberrant activation of mTORC1 in various tissues. Here, we characterize mice with genetic deletion of Tbc1d7, which are viable with normal growth and development. Consistent with partial loss of function of the TSC complex, Tbc1d7 knockout (KO) mice display variable increases in tissue mTORC1 signaling with increased muscle fiber size but with strength and motor defects. Their most pronounced phenotype is brain overgrowth due to thickening of the cerebral cortex, with enhanced neuron-intrinsic mTORC1 signaling and growth. Thus, TBC1D7 is required for full TSC complex function in tissues, and the brain is particularly sensitive to its growth-suppressing activities. Display omitted •A mouse knockout of Tbc1d7 encoding a core component of the TSC complex is presented•Tbc1d7 KO mice display increased tissue mTORC1 signaling but normal development•Tbc1d7 KO mice exhibit brain overgrowth with cortical thickening•Tbc1d7 KO neurons display mTORC1-dependent increases in growth and defects in polarity Schrötter et al. describe a mouse knockout model of TBC1D7, a core component of the tuberous sclerosis complex (TSC) protein complex, which serves as a central brake on mTORC1 signaling and cell and tissue growth. Tbc1d7 KO mice exhibit brain overgrowth associated with an mTORC1-dependent increase in neuronal cell size.