Serine/threonine-protein phosphatase 2A activator

PTPA (serine/threonine-protein phosphatase 2A activator) is a peptidyl-prolyl cis-trans isomerase that functions as a regulatory subunit of PP2A (UniProt: Q15257). It modulates PP2A catalytic activity and substrate specificity through conformational changes, and can reactivate inactive PP2A complexes in an ATP- and Mg²⁺-dependent manner. PTPA also participates in apoptosis through mechanisms independent of PP2A.

PTPA is implicated in neurodegeneration, with variants associated with PARK25 (Parkinson disease 25, autosomal recessive early-onset with impaired intellectual development), characterized by early-onset parkinsonism, developmental delay, and cognitive impairment (UniProt: Q15257). The protein's role in PP2A regulation connects it to phosphatase-dependent cellular signaling pathways.

In Alzheimer's disease, PTPA shows ambiguous directionality across subcellular fractions in human post-mortem brain compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change was 0.291 across three analyzed fractions from a TMT-labeled, four-fraction proteomics study, indicating modest and inconsistent regulation that may vary by cellular compartment.