A role for SOX5 haploinsufficiency in the manifestation of genetic disease in humans was first appreciated by Lamb and colleagues in a 2012 publication [2], describing monoallelic perturbation of SOX5 in 16 individuals with a neurodevelopmental disorder characterized by intellectual disability, speech delay, dysmorphia, behavior problems, and variable other symptoms including motor dysfunction (referred to as Lamb-Shaffer syndrome, MIM616803). This evidence concerns the gene SOX5 and 12p12.1 microdeletion syndrome.