Shank proteins also play a role in synapse formation and dendritic spine maturation.

In an inducible knockout, restoration of SHANK3 expression in adult mice promoted dendritic spine growth and recovered normal grooming behaviour and voluntary social interaction.

Experiments on different developmental windows suggested that early intervention was more effective in restoring behavioural traits.

A rat model of SHANK3 was developed using zinc finger nucleases targeting exon 6 of the ankyrin (ANK) repeat domain.

In humans, 5 patients have been described harboring varying mutations in exon 6 of the SHANK3 protein.