SLITRK1 ("SLIT and NTRK-like family, member 1") is a human gene that codes for a transmembrane and signalling protein that is part of the SLITRK gene family, which is responsible for synapse regulation and presynaptic differentiation in the brain. Expression of the gene has been linked to early formation of excitatory synapses through binding with receptor tyrosine phosphatase PTP (LAR-RPTP). Various studies over the years have linked mutations in the gene to conditions on the OCD spectrum, Tourette syndrome and trichotillomania, however the mutations in the genome itself vary greatly between individuals, with most mutations observed being hard to find in repeat studies. Members of the SLITRK family, such as SLITRK1, are integral membrane proteins with 2 N-terminal leucine-rich repeat (LRR) domains similar to those of SLIT proteins (see SLIT1; MIM 603742). Most SLITRKs, but not SLITRK1, also have C-terminal regions that share homology with neurotrophin receptors (see NTRK1; MIM 191315). SLITRKs are expressed predominantly in neural tissues and have neurite-modulating activity (Aruga et al., 2003). Gene The gene for SLITRK1 is located on chromosome 13q31.1. The gene is expressed only in the brain of humans. The mRNA can differ from alternative splicing, and contains domains for the extracellular matrix as well as for the LRRs. Mice contain an ortholog of the gene called Slitrk1. Protein structure SLITRK1 contains 2 horseshoe shaped leucine rich repeat domains (LRRs) in its extracellular domain which are vital to its function. The LRRs have 6 modules each and are connected by a 70-90 amino acid loops. LRR1 is a more conserved sequence and is present as a dimer while LRR2 is a monomer and has a more variable sequence. The conserved sequence of LRR1 contains critical binding pockets and specific charged residues that are important for it to carry out its function of binding to LAR-RPTPs on the N-terminus. Both LRR sequences are randomly positioned on the protein and contain variable linker regions. The protein also contains a short intracellular domain, but lacks a tyrosine phosphorylation motif which is present in other SLITRK genes. Function SLITKR1 is highly expressed in the central nervous system. It plays a critical part in regulating synapse formation between hippocampal neurons and in differentiation of synapses, helping in neuronal outgrowth. It is expressed during embryonic stages and postnatally but expression decreases over time and is localized to the postsynaptic membrane. Overexpression of SLITKR1 promotes postsynaptic differentiation for excitatory and