The glycine transporter subtype 2 (GlyT2) is localized in axon terminals of glycinergic neurons. Mice deficient in GlyT2 are normal at birth but during the second postnatal week develop a lethal neuromotor deficiency that resembles severe forms of human hyperekplexia (hereditary startle disease) and is characterized by spasticity, tremor, and an inability to right. The amplitudes of glycinergic inhibitory currents (IPSCs) were strikingly reduced in hypoglossal motoneurons from GlyT2 deficient mice. This reduction of IPSC was already evident at early after birth (P1-2). In contrast to other animal models with failure of glycinergic transmission, no compensatory up-regulation of GABAergic IPSCs was observed during postnatal development. Thus, it appears that GlyT2 is crucial for efficient transmitter loading of synaptic vesicles in glycinergic nerve terminals. (Supported by DFG).