Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform

PPP2R5E encodes the 56 kDa regulatory (B) subunit epsilon isoform of protein phosphatase 2A (PP2A), a key modulator of phosphatase substrate specificity and catalytic activity (UniProt: Q16537). By directing the catalytic core enzyme to specific subcellular compartments, this regulatory subunit helps fine-tune dephosphorylation events critical for cellular signaling. PP2A dysfunction has been implicated in neurodegenerative processes through impaired regulation of tau phosphorylation and amyloid precursor protein metabolism.

PPP2R5E is relevant to Alzheimer's Disease pathology. In human post-mortem AD brain tissue compared to age-matched controls, PPP2R5E shows consistent downregulation across subcellular fractions, with a mean log2 fold-change of −0.92 (Chaparral AD proteomics). This reduction in regulatory subunit expression may impair PP2A-mediated dephosphorylation of tau and other AD-associated substrates, potentially contributing to pathological tau accumulation and neurodegeneration characteristic of the disease.