PDE1C is a calmodulin-dependent phosphodiesterase with dual specificity for the second messengers cAMP and cGMP 1. It functions as a key regulator of cyclic nucleotide signaling in multiple tissues, with particularly high expression in cardiac myocytes and vascular smooth muscle cells 23. Mechanistically, PDE1C hydrolyzes both cAMP and cGMP, thereby modulating the amplitude and duration of intracellular signaling cascades 1. In cardiac tissue, PDE1C specifically regulates the nitric oxide-sensitive guanylyl cyclase cGMP microdomain and influences contractility through cAMP/PKA and PI3K/AKT signaling pathways 32. In vascular contexts, PDE1C suppresses calcium influx in pericytes via cAMP/PKA signaling, promoting vasodilation and affecting hemodynamics 4. PDE1C dysregulation is implicated in multiple pathologies. Elevated PDE1C expression contributes to cardiac remodeling and heart failure by promoting myocyte apoptosis and hypertrophy 2. In vascular disease, PDE1C drives abdominal aortic aneurysm development through vascular smooth muscle cell senescence via SIRT1-dependent mechanisms 5. PDE1C is amplified in glioblastoma cells, driving proliferation, migration, and invasion 6. Additionally, PDE1C variants cause autosomal dominant nonsyndromic hearing loss by disrupting cAMP/cGMP cross-talk in inner and outer hair cells 1. Therapeutically, PDE1C inhibition shows promise for cardiac disease, aortic aneurysm, and potentially malignancies.