TMCC2 is located on chromosome 1q32.1 and so is not directly implicated in trisomy 21; putative alteration of TMCC2 neurobiology in Down syndrome may therefore relate to over‐expression of APP, its proteolytic products, or be associated with one or more of the 200–300 other genes present on chromosome 21, which will also be present in excess. This evidence concerns the gene APP and Down syndrome.