JB Special Review—Fundamental Roles of Glycans in Eukaryotes The cytoplasmic peptide:N-glycanase (Ngly1)—basic science encounters a human genetic disorder

Peptide:N-glycanase (PNGase) is a de-N-glycosylating enzyme that cleaves intact N-glycans from glycopro-teins/glycopeptides. The activity of the cytoplasmic PNGase in several mammalian-derived cultured cells was first reported in 1993, and 7 years later, the gene encoding the enzyme was identified in budding yeast. Although the gene—PNG1 in budding yeast and NGLY1/Ngly1 in mammalian cells—appears to be well conserved throughout eukaryotes, the biological significance of this enzyme has remained elusive until recently. However, discovery of a human genetic dis-order involving the NGLY1 gene clearly indicates that this enzyme plays a critical role in human biology. This review summarizes the research history of cytoplasmic PNGase. The importance of curiosity-driven, pure ‘basic science ’ will also be discussed