CLSTN2 (calsyntenin 2) is a postsynaptic cell adhesion molecule that mediates synapse formation and plasticity. It functions as a neurexin-binding protein at the postsynaptic membrane, promoting synapse development and assembly 1. CLSTN2 is expressed in the medial temporal lobe and contributes to episodic memory performance through interactive effects with other genetic variants 2. In episodic memory tasks, CLSTN2 polymorphisms (rs6439886) show interactive effects with KIBRA variants, where the C-allele can enhance memory performance in certain genetic backgrounds but reduces performance in KIBRA C-allele homozygotes 2. This gene-gene interaction effect is particularly pronounced in cognitively compromised populations, such as elderly individuals with depression 3. Beyond neurocognitive functions, CLSTN2 has been identified as a surface marker of midbrain dopaminergic progenitors, enabling enrichment of dopaminergic neurons (up to 80%) for cell-based Parkinson's disease therapies 1. Additionally, CLSTN2 shows genome-wide significant association with HDL-mediated cholesterol efflux capacity, a cardiovascular risk factor 4. CLSTN2 has been identified as a candidate disease gene in genetic screening studies 5, though some studies in elderly cohorts found no significant associations between CLSTN2 polymorphisms and memory decline or hippocampal atrophy 67.