PPEF1 (protein phosphatase with EF-hand domain 1) is a calcium-dependent serine/threonine protein phosphatase that demonstrates dual calcium sensitivity through both its C-terminal EF-hand domains and N-terminal calmodulin-binding IQ motifs 1. The enzyme binds calmodulin in a calcium-dependent manner with nanomolar affinity, suggesting sophisticated regulation by intracellular calcium levels 1. PPEF1 appears to play important roles in neurological processes, as it has been identified as a hub gene associated with Alzheimer's disease pathophysiology 23. In Alzheimer's disease, PPEF1 is linked to autophagy regulation and shows altered expression patterns that correlate with disease progression 24. The gene has also been implicated in cancer biology, where it shows differential expression in various cancer types including breast cancer and stomach adenocarcinoma, suggesting potential roles in tumor progression and immune cell infiltration 56. Additionally, PPEF1 has been identified as a potential therapeutic target in asthma treatment, where it may contribute to airway remodeling processes 7. The protein's unique dual calcium-sensing mechanism distinguishes it from other calcium-dependent phosphatases like calcineurin, positioning it as a specialized regulator of cellular signaling pathways.