LRRC55 modulates BK channels to support Purkinje cell plasticity and motor coordination

Large-conductance Ca²⁺- and voltage-activated K⁺ (BK) channels are widely expressed, including in the brain where they shape neuronal excitability. Their physiological functions are strongly influenced by cell-type-specific auxiliary subunits. The auxiliary γ3 subunit (LRRC55) enhances BK-channel activation by shifting voltage-dependent gating toward more negative potentials; however, its protein distribution and in vivo function remain unclear. Here, we generated knock-in mice carrying a C-terminal epitope tag on endogenous LRRC55 to map its expression, and <i>Lrrc55</i> knockout mice to test its function. LRRC55 protein was selectively enriched in cerebellar Purkinje cells. <i>Lrrc55</i> deletion produced ataxia-like impairments in gait, balance, and coordination. In acute slices, pharmacological BK-channel block with paxilline altered Purkinje cell simple- and complex-spike firing in wild-type mice, whereas these BK-dependent effects were largely absent in <i>Lrrc55</i> knockouts, indicating that LRRC55 is required for BK channels to shape Purkinje cell firing under these conditions. Moreover, LRRC55 loss disrupted cerebellar synaptic plasticity, abolishing parallel fiber-Purkinje cell long-term potentiation and eliminating climbing fiber-Purkinje cell long-term depression, phenocopying paxilline in wild-type cells. Together, these results identify LRRC55 as a Purkinje-cell-enriched auxiliary subunit that is essential for BK-dependent excitability and plasticity and that supports normal cerebellar motor function.