KLHL1 (Kelch-like family member 1) is a brain-specific, neuronal actin-binding protein that functions as a modulator of neuronal excitability through regulation of voltage-gated calcium channels 1. The protein localizes to the soma and dendritic arbors, where it organizes the actin cytoskeleton and participates in neurite outgrowth 2. KLHL1 interacts with P/Q-type (Cav2.1) and T-type (Cav3.2) calcium channel subunits, increasing current density and calcium influx through mechanisms involving both channel number upregulation and alterations in channel kinetics 12. These modulatory effects require the actin-binding kelch domain, highlighting the functional importance of actin interactions 2. In cerebellar Purkinje neurons, KLHL1 is essential for dendritic development; targeted deletion causes dendritic atrophy, abnormal gait, and progressive motor coordination loss 3. KLHL1 also exhibits presynaptic functions, influencing synapsin I levels and synapse number 4. Disease relevance includes spinocerebellar ataxia type 8 (SCA8), where CTG expansions in the overlapping antisense RNA (KLHL1AS) likely suppress KLHL1 expression 5. Additionally, KLHL1 downregulation correlates with dopaminergic neuron dysfunction in Parkinson's disease 6, and genetic variants in KLHL1 are associated with susceptibility to trigger finger 7.