The tuberous sclerosis complex 1/2-mammalian target of rapamycin (TSC1/2-mTOR) proteins act as integrators of a range of intracellular signalling pathways. Various genetic disorders associated with learning and behavioural deficits, including TSC, Fragile X, Neurofibromatosis Type 1, Noonan and Leopard syndromes, are associated with abnormalities in TSC-mTOR signalling. Based on the assumption that signalling proteins and their structural and functional components are widely conserved, a number of animal models are used to study aspects of the physical and behavioural phenotypes of these human disorders. Model organisms include rat (Rattus norvegicus), mouse (Mus musculus), zebrafish (Danio rerio), fruitfly (Drosophila melanogaster) and fission yeast (Schizosaccharomyces pombe). Here we used a bioinformatic approach to examine the presence of structural and functional elements of TSC1 and TSC2 across these organisms, together with Strongylocentrotus purpuratus and Dictyostelium discoideum. Results suggest that while Rattus norvegicus and Mus musculus TSC1 and TSC2 showed very high similarity to the human sequences, this was not the case for Danio rerio, Drosophila melanogaster, Strongylocentrotus purpuratus, Schizosaccharomyces pombe or Disctyostelium discoideum. Findings indicate that caution should be exercised in detailed interpretation of results from some model organisms.