NGLY1-Deficiency and the Non-Lysosomal Degradation of Free N-Glycans

Abstract

Peptide:N-glycanase (PNGase) is a deglycosylating enzyme that acts on asparagine-linked (N-linked) glycans. I was involved in the discovery of this enzyme activity in 1993, as well as the identification of the gene encoding this enzyme in 2000. In 2007, I proposed the existence of a novel “non-lysosomal” glycan degradation pathway in which cytoplasmic PNGase plays pivotal roles. In 2008, I was fortunate to receive a Young Investigator Award from the Japanese Society of Carbohydrate Research. Since that time remarkable progress has been made regarding the functional analysis of the cytoplasmic PNGase (NGLY1 in mammals). After the discovery of a human genetic disorder, an NGLY1-deficiency, caused by the genetic mutations of NGLY1 gene, the functional importance of this enzyme has attracted widespread interest. In this article, I briefly summarize recent research progress on NGLY1.