KCTD7 (potassium channel tetramerization domain containing 7) is a neuronal protein involved in controlling cortical neuron excitability and regulating neurovascular patterning. KCTD7 is enriched in specific brain regions during development and localizes to neurons in the inner retina and cerebellar Purkinje cells, where it is absent from vessels themselves 12. The protein functions in intracellular glutamate homeostasis and membrane hyperpolarization, contributing to proper neural circuit function and the development of precise neurovascular units that support neuronal activity 1. KCTD7 mutations cause progressive myoclonic epilepsy (PME), an autosomal-recessive neurodegenerative disorder typically presenting in infancy with severe, drug-resistant seizures, myoclonus, cognitive regression, and ataxia 34. The disease phenotype is variable; some patients stabilize after several years with long survival, while others experience fatal status epilepticus 35. Additional rare phenotypes include neuronal ceroid lipofuscinosis (CLN14) and opsoclonus myoclonus ataxia syndrome 45. Mechanistically, Kctd7 deficiency causes selective Purkinje cell death, cerebellar microvascular defects, and increased retinal vascular branching with functional impairment 12. Recently, KCTD7 was identified as a novel susceptibility locus for multiple system atrophy, a synucleinopathy, suggesting broader neurodegeneration involvement 6. Over 100 cases with KCTD7 variants have been reported, with both recurrent and novel pathogenic variants identified across diverse populations 784.