NGLY1 is a cytoplasmic N-glycanase widely distributed in eukaryotic cells, and its activity was first reported in Japan in 1993. In 2012, NGLY1 deficiency was reported as a recessive genetic disorder caused by mutations in this gene, and since then, its functional importance has attracted attention. More than 150 patients have been confirmed worldwide to date, and a Japanese patient has also been found. The major symptoms of NGLY1 deficiency are (1) developmental delay and intellectual disability, (2) involuntary movement (mainly hyperkinetic), (3) liver dysfunction (such as transient elevation of serum transaminase levels), (4) alacrima (hypo/alacrima), and (5) peripheral neuropathy. Clinical trials of the AAV9-based gene therapy are currently underway in the United States since 2024.