PRIMA1, the proline-rich membrane anchor 1 gene, encodes a transmembrane protein that anchors acetylcholinesterase (AChE) to the membrane rafts of neurons. AChE hydrolyzes acetylcholine, thus PRIMA1 is involved in cholinergic neurotransmission pathways. This function is crucial for normal neuronal communication and overall nervous system function [1].

A novel splice-site mutation (c.93 + 2T>C) in PRIMA1 was identified in a family with autosomal recessive nocturnal frontal lobe epilepsy (NFLE). Using a minigene system, this mutation was shown to lead to skipping of the first coding exon of the PRIMA1 mRNA, effectively knocking out PRIMA1 function. PRiMA knockout mice also exhibit a reduction of AChE and accumulation of acetylcholine at the synapse. These findings suggest that mutations in PRIMA1 can disrupt cholinergic responses, causing severe NFLE and intellectual disability in this family [1].

In conclusion, PRIMA1 is essential for normal cholinergic neurotransmission by anchoring AChE. The discovery of a PRIMA1-knockout-like effect due to a mutation in a family with NFLE, along with findings in PRiMA knockout mice, highlights its significance in the context of this epilepsy disorder. Understanding PRIMA1's role can potentially lead to new insights into the pathophysiology of NFLE and related neurological conditions.