Glycine receptors (GlyR) are ligand-gated ion channels, selectively allow anions to pass. It plays an important role in inhibitory neurotransmission within the central nervous system mainly in the spinal cord and brainstem. These receptors are integral membrane proteins made up of five subunits and form a chloride-conducting pore. Activation of GlyR by glycine induces hyperpolarization which further helps in regulating the neuronal excitability. Four subunits of α isoforms (1-4) and a β-subunit have been identified. GlyRs are classified into two major forms: heteromeric forms consist of α- and β-subunits and homomeric form is composed only of α subunits. GlyRs are essential for functions such as motor control and pain modulation. Endocytosis of GlyRs is required to maintain receptor turnover and efficient synaptic signaling. This process is either constitutively or stimulated by protein kinase C (PKC) also dependent on dynamin. PKC activation facilitates GlyR internalization through a dileucine motif in the receptor’s cytoplasmic loop; it is a mechanism essential for synaptic plasticity and the regulation of synaptic efficacy. GlyRs are also involved in non-neuronal functions including immune modulation, cytoprotection, and regulation of endothelial cells. Disruptions in GlyR signaling are associated with various neurological and psychiatric disorders, including schizophrenia. Altered GlyR activity contributes to neurotransmission imbalances and associated symptoms. Further detailed understanding of GlyR endocytosis and signaling mechanisms is important for developing therapeutic strategies for these conditions.