GNE is a bifunctional enzyme that catalyzes the rate-limiting step in sialic acid biosynthesis, possessing both UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase activities 1. This enzyme initiates the metabolic pathway leading to production of N-acetylneuraminic acid (NeuAc), a critical precursor for sialic acid synthesis. Sialic acids are negatively charged sugars that reside as terminal components of cell surface glycoconjugates and mediate essential cellular functions including cell adhesion, signal transduction, and cellular recognition. GNE mutations cause autosomal recessive GNE myopathy, a progressive distal myopathy predominantly affecting adult populations and characterized by rimmed vacuoles in muscle fibers 21. GNE myopathy-associated mutations are predominantly missense, resulting in reduced but not absent enzyme activities 3. The pathomechanism likely involves aberrant muscle sialylation due to compromised sialic acid biosynthesis 4. The disease predominantly affects foot flexor muscles initially and predominantly presents in specific populations including Persian Jewish and East Asian communities 1. Current treatment remains supportive, though promising therapeutic trials targeting this metabolic defect are in development 1.