Liprin-alpha-3

Liprin-alpha-3 (PPFIA3) is a 1194-amino-acid scaffolding protein that regulates focal adhesion dynamics and localizes receptor-like tyrosine phosphatases at the plasma membrane, potentially controlling their substrate interactions and extracellular engagement (UniProt: O75145).

PPFIA3 is known from its association with Paul-Chao neurodevelopmental syndrome (NEDPACH, MIM 621122), an autosomal dominant condition presenting with developmental delay, intellectual disability, hypotonia, microcephaly or macrocephaly, autistic features, and epilepsy. This genetic disease link highlights the protein's role in neurodevelopment and neuronal function.

In Alzheimer's disease, PPFIA3 shows reduced abundance in post-mortem AD brain tissue compared to age-matched controls. Quantitative proteomics analysis (TMT labeling, four subcellular fractions) detected a mean log2 fold-change of −0.58, indicating downregulation (Chaparral AD proteomics). The consistent direction across fractions suggests a modest but reproducible decrease in PPFIA3 levels in the AD brain.