In order to understand how epigenetic defects that affect human health could suggest targets for therapeutic interventions, especially for neurological disorders, the Lesch-Nyhan disease (LND) has been selected as a valuable model to study the genetic-epigenetic interplay, especially to explore the epistasis between the housekeeping hypoxanthine phosphoribosyltransferase 1 (HPRT1) and β-amyloid precursor protein (APP) genes. This evidence concerns the gene HPRT1 and nervous system disorder.