PPP1R9A (protein phosphatase 1 regulatory subunit 9A) is an actin cytoskeleton regulator that binds F-actin with cross-linking activity and inhibits protein phosphatase 1-alpha. The gene is involved in neurite formation and dendritic spine development, with expression localized to the postsynaptic density and neuronal projections 1. Mechanism: PPP1R9A regulates actin dynamics through its interaction with NMDA receptor signaling pathways that control spine structure and function 1. The gene's imprinting status varies across species—it is biallelically expressed in pigs and cattle but exhibits tissue-specific monoallelic expression in other mammals 23. Disease Relevance: PPP1R9A mRNA expression is significantly elevated in bipolar disorder subjects and implicated in dendritic spine loss characteristic of schizophrenia and bipolar disorder, potentially through indirect effects on NMDA signaling pathways 1. The gene is also identified as a candidate gene for neurodevelopmental disorders through copy number variation analysis 4 and is upregulated in hepatosplenic T-cell lymphoma and prostate cancer, where it may contribute to altered cell proliferation 56. Clinical Significance: Recent pleiotropy analysis identified PPP1R9A as a shared genetic locus influencing both longevity and muscle weakness in aging populations 7, suggesting broader relevance to age-related phenotypes and potential therapeutic targets for healthy aging.