SLC6A5 encodes glycine transporter 2 (GlyT2), a presynaptic sodium- and chloride-dependent transporter responsible for glycine reuptake and recycling at glycinergic synapses 1. GlyT2 is predominantly expressed in the brainstem, spinal cord, and cerebellum, where it maintains glycinergic neurotransmission by removing glycine from the synaptic cleft 1. Loss-of-function mutations in SLC6A5 impair glycine uptake and cause defective GlyT2 subcellular localization 2, leading to hyperekplexia 3, a rare neurogenetic disorder characterized by neonatal-onset exaggerated startle responses, muscle stiffness, and life-threatening apnea episodes 23. SLC6A5 mutations account for approximately 18.75% of genetically confirmed hyperekplexia cases 3. Animal models with Slc6a5 null alleles exhibit accelerated neuromuscular junction maturation and behavioral abnormalities including hyperactivity and altered grooming, phenotypes observed in schizophrenia models 4. Clinically, hyperekplexia caused by SLC6A5 mutations requires careful differential diagnosis from epilepsy, as antiepileptic drugs are contraindicated 5. Disease-associated mutations include missense, nonsense, and frameshift variants affecting predicted glycine and sodium binding sites 2.