CLPTM1 regulator of GABA type A receptor forward trafficking (CLPTM1)

CLPTM1 is a multi-pass membrane protein that regulates the forward trafficking of GABA type A receptors by binding and trapping these receptors in the endoplasmic reticulum, thereby limiting their expression on the neuronal surface[1][2][3][6]. This modulates synaptic strength and inhibitory neurotransmission, playing a key role in homeostatic plasticity and seizure susceptibility[2][4]. CLPTM1 may function as a lipid scramblase and is also required for efficient inositol deacylation of GPI-anchored proteins in the ER[3][7]. Genetic variants are associated with cleft lip and palate, and alterations in its activity have been implicated in neurological diseases such as epilepsy[1][4].

Other names

CLPTM1Putative lipid scramblase CLPTM1Cleft lip and palate transmembrane protein 1Clef lip and palate associated transmembrane protein 1

Drugs enhancing GABA type A receptor surface expression/activity may be more effective if CLPTM1 is downregulated, as CLPTM1 traps GABA type A receptors in the ER and decreases their membrane expression[2][4].