GPHN (gephyrin) is a multifunctional protein with critical roles in synaptic organization and molybdenum cofactor biosynthesis. Structurally, the GPHN gene spans approximately 800 kb on chromosome 14 with 27 exons, generating 11 distinct transcript isoforms through alternative splicing, with 10 specific to neuronal tissue 1. The protein functions as a peripheral membrane organizer that clusters and localizes inhibitory glycine receptors (GlyR) and GABA(A) receptors to the postsynaptic membrane through interactions mediated by its C-terminal MoeA homology domain 12. Beyond synaptic roles, gephyrin catalyzes two sequential steps in molybdenum cofactor biosynthesis: adenylation of molybdopterin followed by molybdate insertion 3. Mutations in GPHN cause molybdenum cofactor deficiency type C, an autosomal-recessive disorder resulting in combined loss of all molybdoenzyme activities (aldehyde oxidase, xanthine oxidoreductase, sulfite oxidase, and mARC) 3. Clinically, GPHN dysfunction produces progressive neurological damage in early childhood, with phenotypes resembling hyperekplexia (startle disease), though gephyrin mutations are less frequent than glycine receptor alterations in this condition 2. Additionally, the GPHN locus at 14q23.3 contains the FRA14B common fragile site, where focal deletions occur in approximately 5% of cancer cells and germline copy number variants associate with neurodevelopmental disorders including autism spectrum disorder 45.