Lhfpl4, also known as GARLH4, is a tetraspanin that plays a crucial role in the targeting and clustering of synaptic GABAA receptors at inhibitory synapses. It is involved in the regulation of inhibitory synaptic transmission, which is essential for maintaining the balance between excitatory and inhibitory neural activities in the brain [1,2].

In Lhfpl4 knockout mice, there is a cell-type-specific reduction in GABAAR and gephyrin clusters, with large intracellular gephyrin aggregates observed in vivo. GABAARs are still trafficked to the neuronal surface in hippocampal pyramidal neurons but are no longer localized at synapses, leading to a loss of fast inhibitory postsynaptic currents. These mice also display profound impairment of inhibitory synapse formation, prominent motor behavioral deficits, and premature death, highlighting the essential role of Lhfpl4 in inhibitory synapse function and brain development [1,2].

In conclusion, Lhfpl4 is essential for inhibitory synapse function as it regulates the targeting and clustering of synaptic GABAA receptors. The use of Lhfpl4 knockout mouse models has provided valuable insights into the role of Lhfpl4 in inhibitory synapse formation and related motor behavior, which may have implications for understanding neurological disorders associated with impaired inhibitory synaptic function [1,2].

References:

1. Davenport, Elizabeth C, Pendolino, Valentina, Kontou, Georgina, Farrant, Mark, Kittler, Josef T. . An Essential Role for the Tetraspanin LHFPL4 in the Cell-Type-Specific Targeting and Clustering of Synaptic GABAA Receptors. In Cell reports, 21, 70-83. doi:10.1016/j.celrep.2017.09.025. https://pubmed.ncbi.nlm.nih.gov/28978485/

2. Wu, Min, Tian, Hong-Lei, Liu, Xiaobo, Du, Shengwang, Xia, Jun. . Impairment of Inhibitory Synapse Formation and Motor Behavior in Mice Lacking the NL2 Binding Partner LHFPL4/GARLH4. In Cell reports, 23, 1691-1705. doi:10.1016/j.celrep.2018.04.015. https://pubmed.ncbi.nlm.nih.gov/29742426/