Loss of Shank3, a major scaffolding protein at glutamatergic synapses (Monteiro and Feng, 2017), is strongly associated with Phelan-McDermid syndrome and autism spectrum disorders (ASDs; Leblond et al., 2014; Costales and Kolevzon, 2015), and is required for normal hippocampal LTP (Bozdagi et al., 2010; Song et al., 2019), and the expression of homeostatic and ocular dominance plasticity within V1 (Tatavarty et al., 2020; Wu et al., 2022). Here, SHANK3 is linked to Phelan-McDermid syndrome.