NGLY1 (N-glycanase 1) is a cytosolic deglycosylating enzyme that removes N-linked glycans from misfolded glycoproteins destined for proteasomal degradation 1. Mechanistically, NGLY1 cleaves the beta-aspartyl-glucosamine linkage between N-glycans and asparagine residues, converting asparagine to aspartate and enabling subsequent proteasome-mediated degradation through endoplasmic reticulum-associated degradation (ERAD) 12. Beyond canonical deglycosylation, NGLY1 functions as an 'editing enzyme' that modulates target protein function by introducing negative charges through asparagine-to-aspartate conversion 1. NGLY1 also regulates the transcription factor NFE2L1, which controls proteasomal gene expression and oxidative stress responses 32. Biallelic NGLY1 mutations cause congenital disorder of deglycosylation 1 (CDDG1), a rare autosomal recessive disorder affecting over 100 individuals with >70 distinct pathogenic variants 2. Patients exhibit multisystemic features including global developmental delay, microcephaly, peripheral neuropathy, hypotonia, hypolacrima/alacrima, hypertransaminasemia, and feeding difficulty 24. NGLY1 deficiency impairs proteasomal gene expression and alters ribosome biogenesis pathways 5. Currently, no approved therapy exists for NGLY1 deficiency, though FDA-approved drug repurposing screens have identified potential candidates to ameliorate disease phenotypes 6.