In this manuscript, we review the importance of PEG10 and PEG11/RTL1 in genomic imprinting research via their functional roles in development and human disease, including neurodevelopmental disorders of genomic imprinting, Angelman, Kagami-Ogata and Temple syndromes, and the impact of newly inserted DNA on the emergence of newly imprinted regions. The gene discussed is RTL1; the disease is motor developmental delay due to 14q32.2 paternally expressed gene defect.