Table 2.

List of the proteins and signaling pathways affected by NGLY1 deficiency in various model systems.

Associated Proteins or Signaling Pathways	Role of NGLY1	References
ERAD pathway	Deglycosylation of misfolded proteins	Hirsch et al., 2003 [67] Grotzke et al., 2013 [71] Hosomi & Suzuki, 2015 [68] Hosomi et al., 2016 [74]
BMP signaling (BMP4/Dpp)	Deglycosylation and retrotranslocation of misfolded BMP4/Dpp	Galeone et al., 2017 [55] Galeone et al., 2020 [40]
AMP kinase signaling and mitochondrial structural integrity	Regulation of AMPKα mRNA level	Han et al., 2020 [99]
Proteasomal homeostasis	Regulation of proteasomal bounce-back response by deglycosylation and activation of NFE2L1	Lehrbach et. al., 2016 [60] Tomlin et al., 2018 [94]
Resistance to hypotonic cell lysis	Non-enzymatic transcriptional regulation of aquaporin expression, in part through ATF1/CREB1	Tambe et al., 2019 [154]
Na+, K+, 2Cl– ion transport	Regulation of NKCC1 function, potentially through NKCC1 deglycosylation	Talsness et al., 2020 [152]
Mitophagy and mitochondrial homeostasis	Regulation of mitochondrial biogenesis and mitophagy-related gene expression by deglycosylation and activation of NFE2L1	Yang et al., 2018 [44]
Innate immune signaling	Suppression of interferon signaling, at least in part through the DNA-sensing cGAS-STING pathway	Yang et al., 2018 [44] Zolekar et al., 2018 [110]
Melanoma survival and growth	Suppression of stress-signaling-associated apoptosis and cytokine surge	Zolekar et al., 2018 [110]
Ferroptosis	Resistance to ferroptosis through NFE2L1 deglycosylation	Forcina et al., 2022 [100]