Cntn2, also known as Contactin-2 or TAG-1, is a neuronal recognition molecule of the immunoglobulin superfamily. It is involved in crucial biological processes such as axon guidance, neuronal migration, and fasciculation [1,2]. It forms transient homophilic interactions, and its structure reveals a T-shaped homodimer [1]. It may be part of pathways related to neural circuit development, and genetic models can be used to study its functions in depth.

In a mouse model where EGFP was expressed under the Tag-1 promoter and Diptheria Toxin subunit A was used to ablate CNTN2+ cortical neurons, significant defects were observed. These included a smaller cortex, reduction of corticothalamic axons, and callosal and commissural defects, suggesting its importance in neocortical size and axonal tract formation during development [2]. In Drosophila, loss of CNTN2, a predicted protective modifier, rescued loss of PIGA in a PIGA-CDG model, as well as patient-relevant phenotypes like seizures and climbing defects, indicating its role as a genetic modifier in this rare congenital disorder [3].

In conclusion, Cntn2 is vital for processes like axon guidance, neuronal migration, and fasciculation. The use of gene-knockout models in mice and Drosophila has revealed its role in neocortical development and as a genetic modifier in PIGA-CDG. These findings contribute to our understanding of normal neural development and the pathogenesis of related disorders.