RIT2 (Ras like without CAAX 2) is a neuronal GTPase belonging to the Ras superfamily that functions as a critical regulator of dopaminergic signaling and cellular processes. RIT2 binds and exchanges GTP and GDP, and directly interacts with the dopamine transporter (DAT) to modulate dopamine reuptake through protein kinase C-stimulated endocytic trafficking 1. Additionally, RIT2 modulates activation of POU4F1 as a gene expression regulator and participates in intracellular signal transduction pathways, including regulation of Cdc42 protein signaling and positive regulation of the MAPK cascade. RIT2 is a well-established susceptibility gene for Parkinson's disease (PD), with the rs12456492 G allele conferring increased PD risk across multiple populations 2. Transcriptomic profiling identified RIT2-enriched neurons in the substantia nigra as a vulnerable cell type in PD, with reduced RIT2 expression implicated in disease pathogenesis 3. Beyond PD, RIT2 variants are associated with schizophrenia and autism 4. RIT2 also represents a proteomic therapeutic target in smoking behavior, with genetic liability for smoking-associated RIT2 inversely linked to longevity 5. Conditional dopaminergic RIT2 knockdown studies reveal sex-specific roles in cocaine sensitivity and striatal circuit function, demonstrating RIT2's importance for dopamine-dependent behaviors 6. These findings establish RIT2 as a multifunctional regulator of dopaminergic neurotransmission with significant relevance to neuropsychiatric disease pathogenesis.