Lrfn5, a member of the leucine-rich repeat and fibronectin III domain-containing (Lrfn) family, is a neuronal transmembrane protein. It is involved in regulating neural development and synaptic function [1,2,3,4,5,6]. Lrfn5 has a leucine-rich repeat (LRR)-immunoglobulin-like (Ig)-fibronectin type III (Fn)-transmembrane domain structure and is expressed in mature neural cells in the developing nervous system [6].

Recent studies have implicated Lrfn5 in several neuro-psychiatric disorders. In major depressive disorder (MDD), serum concentrations of Lrfn5 are higher in drug-naive MDD patients compared to healthy controls, and lower in drug-treatment MDD patients. It shows potential as a biomarker for MDD, and its levels are associated with clinical data [1]. Regarding autism, the Lrfn5 locus structure is associated with autism, and a specific locus haplotype maternally inherited segregates with an identical type of autism in males. Also, Lrfn5 dysregulation could be an epigenetic cause of autism [2]. In a patient with autism spectrum disorder, a microdeletion affecting the pseudogene chr14.232.a led to decreased Lrfn5 expression, suggesting the role of long non-coding RNAs in regulating its expression [4]. In another case of a severely autistic girl, a translocation led to a 10-fold reduction in Lrfn5 expression, speculating its contribution to the patient's autism [5].

In conclusion, Lrfn5 is crucial for neural development and synaptic function. Studies on Lrfn5, especially through cases related to neuro-psychiatric disorders like MDD and autism, have revealed its potential role in the pathophysiology of these diseases. Understanding Lrfn5 can provide insights into the mechanisms of these disorders and potentially lead to new diagnostic and therapeutic strategies.