Tyrosine phosphorylation is a powerful mechanism of modulation for proliferation, differentiation, and functioning of neurons. The protein products of the neuronal mouse gene PTPRR are physiological regulators of mitogen-activated protein kinase (MAPK) activities. PTPRR(-/-) mice display deficits of motor coordination and balance skills. PTPRR gene orthologues are found in many vertebrates. Recent observations suggest that the human episodic ataxia 2 (EA2) and spinocerebellar ataxia types 6 (SCA6), 12 (SCA12), and 14 (SCA14) might be associated with impaired phosphorylation levels of cerebellum calcium channels and receptors. The concept that MAPK signaling is a key process in tuning synaptic plasticity in cerebellar circuits is now emerging, with numerous implications for understanding cerebellar functions and cerebellar disorders.