Lipoma HMGIC fusion partner-like 4 protein (LHFPL4)

Lipoma HMGIC fusion partner-like 4 protein (LHFPL4) is a member of the tetraspanin superfamily and acts as a transmembrane accessory protein that interacts with GABAA receptor subunits and neuroligin 2. LHFPL4 is highly enriched at inhibitory postsynaptic sites and is essential for the synaptic clustering and stabilization of GABAA receptors, particularly in excitatory hippocampal pyramidal neurons. Its genetic deletion disrupts GABAA receptor localization at synapses, resulting in profound loss of fast inhibitory postsynaptic currents and alterations in inhibitory signaling, while leaving surface trafficking and excitatory synaptic function intact. LHFPL4's highly specific role is primarily in synaptic scaffolding and stabilization of inhibitory signaling, and it is not directly targeted by current drugs or used as a clinical biomarker. Disruption of LHFPL4 function has been associated with increased seizure susceptibility and motor dysfunction in some preclinical models, highlighting its potential relevance in neuropsychiatric disease mechanisms.

Other names

LHFPL tetraspan subfamily member 4GARLH4GABAA receptor regulatory Lhfpl4LHFP-like protein 4

none directly known; indirect mechanisms likely involve modulation of synaptic GABAA receptor abundance, possibly affecting response to GABAergic drugs