Chn2, encoding β2-chimaerin, is a Rac-specific guanosine-5'-triphosphatase activating protein. It plays a crucial role in establishing functional brain circuitry by controlling axon pruning via the Rac-GTPase system [1,3]. This process is vital for the proper formation of nervous circuits.

Genetic studies have revealed its associations with various conditions. The methylation of the Chn2 gene promoter is significantly correlated with methamphetamine dependence, with the methylation level in the case group being much higher than that in the control group [1]. A novel polymorphism (rs186911567) of the Chn2 gene is associated with smoking [3]. Also, a SNP (rs39059) from the CPVL/Chn2 locus is associated with diabetic retinopathy in Chinese type 2 diabetic patients [2]. In a case of severe insulin resistance and intrauterine growth deficiency, disruption of Chn2 along with INSR was implicated, suggesting Chn2 as a key element of proximal insulin signaling in vivo [4].

In conclusion, Chn2 is essential for the formation of nervous circuits through axon pruning. Its genetic variations and promoter methylation changes are associated with substance dependence, smoking, diabetic retinopathy, and insulin-related growth disorders. Research on Chn2 provides insights into the molecular mechanisms underlying these diseases, potentially guiding the development of targeted therapeutic strategies.