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 Lrrc55 knockout mice to test its function. LRRC55 protein was selectively enriched in cerebellar Purkinje cells. Lrrc55 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 Lrrc55 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.