Lrfn5, also known as Leucine-rich repeat and fibronectin type III domain-containing protein 5, is a regulator of synaptic development. It is involved in neural development and synaptic function, and is located in a 5.4 Mb mammalian-specific conserved topologically associating domain (TAD) [2].

Lrfn5 has been implicated in several disorders. In major depressive disorder (MDD), serum concentrations of Lrfn5 are considerably higher in MDD patients compared to healthy controls, and lower in drug-treatment MDD patients than in drug-naive MDD patients. It is associated with clinical data and may be implicated in the pathophysiology of MDD, with a combination of Lrfn5 and OLFM4 potentially offering a diagnostic biomarker panel for MDD [1]. In autism, the Lrfn5 locus structure is associated with autism, influenced by the sex of the individual and locus conversions. A specific locus haplotype inherited maternally segregates with an identical type of autism in distantly related males, and there is a male/female quantitative difference in the amount of histone-3-lysine-9-associated chromatin around the Lrfn5 gene [2]. Also, in a patient with autism spectrum disorder, a microdeletion affecting the pseudogene chr14.232.a led to decreased Lrfn5 expression, suggesting a role of long non-coding RNAs in regulating its expression [3].

In conclusion, Lrfn5 is crucial for synaptic development and neural function. Studies related to Lrfn5 in MDD and autism through genetic and expression-based analyses have provided insights into its role in these disorders. Understanding Lrfn5 could potentially offer new diagnostic and therapeutic avenues for these neuro-psychiatric conditions.