SH3 and multiple ankyrin repeat domains 3 (SHANK3), a member of the Shank gene family, plays a role in synapse formation and dendritic spine maturation. Shank proteins (Shank 1-3) containing PDZ domains are scaffold proteins of the postsynaptic density (PSD) that connect neurotransmitter receptors and ion channels proteins to the actin cytoskeleton and G-protein-coupled signaling pathways. Transcript splice variation in the Shank family influences the spectrum of Shank-interacting proteins in the PSDs of adult and developing brain to ensure normal development. Mutations of SHANK3 are a cause of autism spectrum disorder (ASD) and the neurological symptoms of 22q13.3 deletion syndrome.