Evidence that the TLDc domain is essential to normal human brain development and function has been highlighted recently by the identification of mutations in the TLDc domain of TBC1D24 in patients with myoclonic, focal or generalized epilepsy, DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation and seizures) syndrome and lethal early-onset epileptic encephalopathy (Balestrini et al. 2016; Campeau et al. 2014a, b; Mucha et al. 2015). This evidence concerns the gene TBC1D24 and DOORS syndrome.