KCTD3 is an accessory subunit that specifically regulates the hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3). KCTD3 directly interacts with HCN3 through the channel's C-terminal domain, profoundly increasing cell surface expression and current density without affecting the channel's voltage dependence or kinetics 1. KCTD3 is widely expressed in brain and kidney tissues 2, where it likely participates in ion channel modulation and cellular signaling. Biallelic loss-of-function mutations in KCTD3 cause a distinct neurological syndrome characterized by developmental epileptic encephalopathy, global developmental delay, central hypotonia with progressive peripheral hypertonia, and posterior fossa abnormalities including cerebellar vermis hypoplasia and Dandy-Walker malformation 2. KCTD3 mutations have been identified as disease-causing in consanguineous families through exome sequencing studies 34. The gene has also been associated with lateral ventricular enlargement in childhood, a structural brain abnormality linked to schizophrenia risk 5, and may contribute to neurodevelopmental disorders when deleted in conjunction with other genomic aberrations 6. KCTD3 represents an important member of the KCTD protein family implicated in neurodevelopmental and neuropsychiatric disorders 7.