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These models can be established from a patient's own cells and can be genetically engineered to generate isogenic, controlled systems for mechanistic studies. Given the challenges of obtaining and working with primary human brain tissue, these models fill a critical gap in our understanding of normal and abnormal human brain development and provide an important complement to animal models. Recently, there has been major progress in modeling the neuropathophysiology of the canonical \u201cmTORopathy\u201d tuberous sclerosis complex (TSC) with such approaches. Studies using two\u2010 and three\u2010dimensional cultures of human neurons and glia have provided new insights into how mutations in the <jats:italic>TSC1<\/jats:italic> and <jats:italic>TSC2<\/jats:italic> genes impact human neural development and function. 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