Lrrc4, also named netrin-G ligand 2 (NGL-2), is a member of the NetrinGs ligands family and the leucine-rich repeat superfamily. It is highly and specifically expressed in the brain. Lrrc4 is involved in multiple important biological functions, regulating the formation of excitatory synapses, promoting axon differentiation, and playing a role in the development of the nervous system. It also participates in complex regulatory loops involving microRNAs, transcription factors, and gene methylation modification [1,2,4].

In experimental autoimmune encephalomyelitis (EAE) mouse models, Lrrc4 knockout leads to quickened and exacerbated disease progression, more severe myelin degeneration, and leukocyte infiltration into the spinal cords. This is accompanied by increased NF-κB p65 activation, altered cytokine levels, and a more severe Th1 immune response. Ectopic expression of Lrrc4 alleviates EAE symptoms and protects neurons from immune damage, suggesting its neuroprotective role [2]. In glioblastoma research, Lrrc4 knockout leads to disordered RAP1GAP gene expression and increased cellular movement, while re-expression can suppress tumors [3].

In conclusion, Lrrc4 is crucial for the normal development of the nervous system and has significant implications in various disease conditions. Gene knockout mouse models, like those in EAE and glioblastoma studies, have revealed its roles in neuro-protection and tumor suppression, highlighting its potential as a therapeutic target in multiple sclerosis and glioblastoma [2,3].