PTPA (protein phosphatase 2 phosphatase activator) is a regulatory subunit that modulates the activity of protein phosphatase 2A (PP2A), a major serine/threonine phosphatase in the brain 1. PTPA functions as a peptidyl-prolyl cis-trans isomerase that catalyzes proline isomerization and acts as a conformational regulator of the PP2A catalytic subunit, reversibly stimulating phosphotyrosyl phosphatase activity in an ATP and Mg2+-dependent manner 2. PTPA can reactivate inactive PP2A complexes and also promotes apoptosis through mechanisms independent of PP2A function 3. Clinically, biallelic PTPA variants cause autosomal recessive early-onset parkinsonism with intellectual disability 1. Identified mutations (p.Ala171Asp and p.Met298Arg) reduce PTPA RNA and protein stability, leading to decreased PP2A complex levels and impaired phosphatase activation 1. PTPA knock-down in Drosophila neurons impairs locomotion in an age-dependent manner, fully reversed by L-DOPA treatment, suggesting a role in dopaminergic pathways 1. Beyond neurological disease, PTPA variants associate with altered metabolic homeostasis, with genetic associations identified between PTPA variants and succinylcarnitine levels in aging populations 4. These findings indicate PTPA dysregulation contributes to neurodegeneration through impaired PP2A-mediated regulation of disease-relevant proteins including alpha-synuclein, tau, and LRRK2 1.