Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform

Summary

PPP2R1A encodes the 65 kDa regulatory subunit A alpha isoform of protein phosphatase 2A (PP2A), which functions as a scaffolding molecule coordinating assembly of the catalytic subunit PP2CA with variable regulatory B subunits (UniProt: P30153). The protein mediates dephosphorylation of multiple substrates including tau/MAPT and AKT1, and serves critical roles in chromosome segregation, transcriptional quality control via the INTAC complex, and regulation of signaling pathways including Hippo and MAPK.

PPP2R1A is widely expressed and participates in diverse biological processes encompassing cell growth, differentiation, apoptosis, and immune regulation through its function in STRIPAK and INTAC multi-protein complexes (UniProt: P30153). Pathogenic variants cause Houge-Janssens syndrome 2, an autosomal dominant neurodevelopmental disorder featuring developmental delay, hypotonia, and intellectual disability.

In Alzheimer's disease, PPP2R1A shows ambiguous regulation across subcellular fractions of post-mortem AD brain tissue (Chaparral AD proteomics). The mean log2 fold-change is −0.1578, suggesting modest downregulation or variable changes depending on cellular compartment. Given PP2A's established role in tau dephosphorylation, dysregulation of this scaffolding subunit may have mechanistic relevance to tau pathology in AD, though the direction of change requires further characterization across brain regions and disease stages.