Neuronal restrictive silencing factor (NRSF), also known as repressor element-1 silencing transcription factor (REST), a Kruppel-type zinc finger protein, functions as a transcription regulator of a myriad of target genes through binding to a specific DNA sequence (repressor element-1/neuron-restrictive silencer element, RE-1/ NRSE). REST differentially influences target-gene expression through interaction with a wide variety of cellular cofactors in a context-dependent manner. Perturbations in the levels and functions of REST lead to various disorders. Recent studies have shown that REST is involves in multiple physiological processes such as maintaining pluripotency and self-renewal of embryonic stem cell and regulating the differentiation of stem cells into neuron or islet cells. The current understanding of NRSF/REST was presented, focusing on its roles in embryonic stem cell self-renewal, early embryonic development, neuron and islet cells diffentiation of stem cells.