NECAP1 (NECAP endocytosis associated 1) is a clathrin-accessory protein primarily involved in clathrin-mediated endocytosis, particularly regulating synaptic vesicle recycling 1. The protein is highly enriched in the central nervous system and localizes to neuronal clathrin-coated vesicles 2, where it modulates synaptic vesicle dynamics through its interaction with clathrin-coated pits and vesicles 3. NECAP1 contains a conserved WXXF motif critical for its endocytic function 2. Loss of NECAP1 function causes Developmental and Epileptic Encephalopathy 21 (EIEE21), characterized by early infantile-onset seizures, developmental delay, severe hypotonia, microcephaly, delayed myelination, and brain abnormalities 4. Both truncating mutations and missense variants trigger pathogenic effects; truncating variants activate nonsense-mediated decay, while missense mutations impair protein function 21. The seizure mechanism likely involves impaired synaptic vesicle recycling, linking endocytic trafficking to epileptogenesis 2. Beyond neurology, NECAP1 DNA methylation patterns in maternal blood associate with offspring birthweight, suggesting involvement in maternal-fetal metabolic processes 5. Mutations in NECAP1 also cause progressive retinal atrophy in dogs, indicating evolutionary conservation of retinal function 3.