Losing the Beat: Contribution of Purkinje Cell Firing Dysfunction to Disease, and Its Reversal

•Purkinje cells are the principle cells of the cerebellum, and fire intrinsically with high frequency and regularity.•A number of diseases converge at least in part on a common functional pathology: Purkinje cell intrinsic firing deficits.•Purkinje cell intrinsic firing deficits typically present peri-onset of behavioral dysfunction, and precede cell loss.•Therapeutic strategies that rescue intrinsic firing deficits often improve behavioral deficits.•Thus we posit that Purkinje cell intrinsic firing deficits is a promising therapeutic target for multiple diseases.