PDE1A is a calcium/calmodulin-dependent cyclic nucleotide phosphodiesterase with dual specificity for cGMP and cAMP, demonstrating preferential efficiency toward cGMP 1. The gene encodes multiple splice variants with tissue-specific expression patterns, particularly enriched in brain, kidney, liver, and testis 1. PDE1A exists as a stable complex with calmodulin in human spermatozoa and functions in regulating intracellular cyclic nucleotide levels 2. Mechanistically, PDE1A hydrolyzes cGMP to suppress protein kinase G (PKG) signaling and subsequent phosphorylation of downstream effectors including vasodilator-stimulated phosphoprotein (VASP) and β-catenin 34. In cancer contexts, PDE1A interacts with the RNA-binding protein YTHDF2 to modulate STAT3 pathway activation and promote metastasis 5. Clinically, PDE1A elevation associates with disease progression across multiple conditions. In diabetic kidney disease and IgA nephropathy, elevated PDE1A correlates with deteriorating renal function and serves as a diagnostic biomarker 63. PDE1A knockout or inhibition with ITI-214 significantly alleviates renal fibrosis in mouse models 3. In cancer, PDE1A overexpression promotes metastasis in triple-negative breast cancer and non-small cell lung cancer through multiple signaling pathways 45. Mendelian randomization analysis suggests PDE1A association with autism spectrum disorder risk 7.