However, BK channel downregulation may be an upstream pathogenic event as TLR4 knockout was also associated with lower cytoCa2+, mitochondrial damage, loss of synaptic inputs from CFs and PFs, diminished dendritic arborization, and impaired spine development, changes that may lead to loss of PN function, degeneration, and ultimately to cerebellar ataxia (Fig. 8). This evidence concerns the gene TLR4 and aceruloplasminemia.