CACNA1D and Parkinson disease: Figure 8 provides a hypothesis of the effects of alterations in CaV1.3 function due to the gain-of-toxic function of LRRK2G2019S kinase in PD. Dysregulation of the channels can disrupt intracellular Ca2+ homeostasis, probably by altering their role in the pacemaker activity of dopaminergic neurons. When Ca2+ clearance systems become overwhelmed, the previously mentioned changes can result in significant alterations in cellular metabolism and elevated production of reactive oxygen species.