Commonly used models are often based on single-gene disorders associated with ASD, such as Tuberous Sclerosis (TSC) and Fragile X syndrome [14, 15], or high-effect risk genes like SHANK3, NLGN3, and NLGN4, as they offer high construct validity and thereby increase relevance [12, 16–18]. Here, SHANK3 is linked to tuberous sclerosis.