Leucine-rich repeat transmembrane neuronal protein 3 (LRRTM3)

Leucine-rich repeat transmembrane neuronal protein 3 (LRRTM3) is a neuron-specific, multifunctional type I transmembrane protein primarily expressed in the brain, especially in cortical laminae and the dentate gyrus[1][4]. It is a member of the LRRTM family of synaptic cell-adhesion molecules within the leucine-rich repeat superfamily, and functions in excitatory synapse development, organization, and maintenance, particularly within hippocampal circuits[3][4]. LRRTM3 regulates presynaptic assembly, activity-dependent synaptic connectivity, and plasticity of mossy fiber–CA3 synapses, as well as modulating glutamatergic neurotransmission[1][3][4]. Unique among LRRTM family members, LRRTM3 plays a role in amyloid precursor protein processing by β-secretase, linking it to amyloid-beta formation and neurodegenerative diseases such as Alzheimer’s disease; genetic associations have also connected LRRTM3 to autism spectrum disorder[1][4][5]. The protein exists in multiple isoforms that differ in cytoplasmic domain and PDZ-binding motifs, suggesting interaction with synaptic scaffolding proteins. No approved drugs are listed as directly targeting LRRTM3, and it is not a clinical biomarker or conventional therapeutic target to date.

Other names

LRRTM3leucine-rich repeat transmembrane neuronal 3UNQ803/PRO1693LRRT3