DOC2A is a calcium-sensing protein that regulates synaptic vesicle fusion and neurotransmitter release. As a C2 domain-containing protein, DOC2A binds calcium and phospholipids, translocating to plasma membranes upon calcium elevation 1. It responds to submicromolar calcium concentrations (half-maximal translocation at ~450 nM) with kinetics suited for modulating short-term synaptic plasticity 1. DOC2A functions as a presynaptic calcium sensor regulating both spontaneous and evoked neurotransmitter release, potentially through interaction with UNC13A and the SNARE machinery protein Munc18-1 2. DOC2A dysfunction is implicated in multiple neurological disorders. Expression is significantly elevated in temporal lobe epilepsy, localizing to presynaptic terminals 3. Heterozygous DOC2A loss-of-function increases seizure susceptibility and causes hyperactivity and macrocephaly when combined with fam57ba haploinsufficiency in the 16p11.2 region 4. A schizophrenia-associated synonymous variant (rs3935873) generates an alternative DOC2A isoform (DOC2A∆Val217-Pro218) that alters excitatory synaptic transmission and produces behavioral deficits 5. Additionally, DOC2A is identified as a shared genetic risk factor between Parkinson's disease and Lewy body dementia 6, 7, suggesting broader neurodegeneration involvement. Reduced Munc18-1 levels destabilize and misdirect synaptic DOC2A 2, linking DOC2A dysfunction to STXBP1 encephalopathies.