Autosomal recessive loss-of-function mutations in N-Glycanase 1 (NGLY1) cause NGLY1 deficiency, the only known human disease of deglycosylation. Patients with NGLY1 deficiency display developmental delay, movement disorder, hypotonia, and alacrima. NGLY1 is a conserved component of the endoplasmic reticulum associated degradation (ERAD) pathway. ERAD is responsible for degrading misfolded proteins that accumulate in the ER lumen under ER stress conditions. NGLY1 deglycosylates misfolded proteins in the cytoplasm as they are translocated from the ER lumen for degradation. While little is known about the pathogenesis underlying NGLY1 deficiency, it is thought that loss of NGLY1 activity results in accumulation of highly N-glycosylated misfolded proteins in the cytoplasm, acting as a ‘sink’ for free UDP-GlcNAc. In turn, this might deplete the circulating pool of free UDP-GlcNAc in the cell, resulting in disease. We hypothesized that restoring the levels of UDP-GlcNAc in the cells might rescue some of the phenotypes associated with NGLY1 deficiency. We used ubiquitous RNAi knockdown of Pngl (Drosophila ortholog of NGLY1) to model complete loss of NGLY1 activity seen in human patients. We show that supplementing the normal diet with GlcNAc can rescue lethality associated with loss of Pngl activity. When raised on normal food, without GlcNAc supplementation, we observed significant lethality, with eclosion of only 18% of expected Pngl knockdown adults. Pngl knockdown lethality occurs throughout larval and pupal development. When diet is supplemented with 100 ug/ml of GlcNAc, we observed significant rescue of the developmental lethality, raising the adult Pngl knockdown eclosion rate to nearly 70%. We also demonstrate that genetic alterations in the ERAD and cytoplasmic heat shock pathways can influence the lethality of Pngl knockdown. Finally, we provide evidence that GlcNAc rescue of lethality likely functions through the ERAD and cytoplasmic heat shock pathways. These data provide a plausible pathophysiology for NGLY1 deficiency. More importantly, our study points to a potential therapy through a simple diet supplement.