The enzyme N-glycanase 1 (NGLY1) is considered a component of the endoplasmic 
reticulum-associated degradation (ERAD) machinery and clinical manifestations of 
its dysfunction include global developmental delay, a movement disorder, 
peripheral neuropathy, liver disorders, microcephaly, diminished reflexes and 
seizures. Although several mutations in NGLY1 have been identified, the relation 
between the defected protein and the above described pathologies is yet unknown. 
We hypothesised that NGLY1 failure to degrade certain proteins may result in 
their accumulation and overexpression and used a systems biology approach to 
identify proteins that may be affected by NGLY1 deficiency. Genes that interact 
with the NGLY1 gene according to BioGRID database of physical and genetic 
interactions were analysed with STRING Protein-Protein interaction database. 
Network analysis identified FAF1 (Fas-Associated Factor 1), an 
apoptosis-potentiating protein, as a possible degradation substrate of NGLY1. 
Examination of normal tissue microarrays demonstrated that FAF1-to-NGLY1 ratio 
is maximal (more than 3:1) in skeletal muscle and brain tissues microarrays. 
This evidence may explain the pathologies in brain and muscle tissues of 
patients with mutated NGLY1. To test this hypothesis, laboratory studies that 
will assess if FAF1 protein is overexpressed in tissues of patients with mutated 
NGLY1 are required.