CACNA1I encodes CaV3.3, a low-voltage-activated T-type calcium channel that mediates calcium ion entry into excitable cells and regulates neuronal excitability, sensory processing, sleep, and neurotransmitter release 1. The channel exhibits unique electrophysiological properties essential for thalamic reticular nucleus pacemaking and thalamocortical network rhythmogenesis 2. Mutations in CACNA1I cause neurodevelopmental disorders through gain- and loss-of-function mechanisms. De novo missense variants, particularly those affecting the channel's activation gate at the cytoplasmic IIS6, IIIS5, and IIIS6 segments, predominantly produce gain-of-function effects characterized by hyperpolarizing shifts in voltage-dependence of activation/inactivation, slowed inactivation kinetics, and increased calcium influx 13. This calcium toxicity and neuronal hyperexcitability explain the phenotypic spectrum ranging from developmental delay and intellectual disability to severe neurodevelopmental disease with seizures 13. Notably, some loss-of-function variants cause developmental delay without seizures 3. CACNA1I variants are associated with schizophrenia risk through altered channel function and dysregulated expression 456. Reduced CaV3.3 function may protect against schizophrenia in some cases 6. T-type channel blockers represent a viable treatment option for CACNA1I-related neurodevelopmental disorders 2.