ERC2 (ELKS/RAB6-interacting/CAST family member 2) is a critical active zone protein that organizes the cytomatrix at nerve terminal active zones to regulate neurotransmitter release 1. ERC2 physically interacts with voltage-dependent Ca²⁺ channels (VDCCs), specifically the β₄-subunit, and modulates channel activation by shifting voltage dependence toward hyperpolarizing directions 2. This interaction may regulate neurotransmitter release by modifying VDCC opening at presynaptic active zones 2. The protein's self-assembly is regulated by serine-arginine protein kinase SRPK2, which controls ERC2 integration during active zone formation through its coiled-coil domains 3. ERC2 recruits liprin-alpha proteins to active zones, with coexpression redistributing liprin-alpha1 to synaptic sites, suggesting a role in presynaptic organization 1. Beyond its synaptic functions, ERC2 shows broader physiological relevance. DNA methylation at ERC2 loci is associated with ADHD symptoms from birth, with one CpG site (cg01271805) in its promoter region showing correlation between peripheral blood and brain methylation 4. Additionally, ERC2 mutations contribute to disease pathogenesis, with the L309I mutation enhancing angiogenesis in Maffucci's syndrome 5, and altered ERC2 expression occurring in multiple sclerosis brain tissue 6.