AKAP12 (A-kinase anchoring protein 12) is a scaffolding protein that mediates subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC), controlling spatiotemporal signaling specificity 1. The protein functions as a negative mitogenic regulator 2 and serves multiple physiological roles including cytoskeletal regulation, endothelial integrity maintenance, and blood-brain barrier formation 2. Mechanistically, AKAP12 nucleates signaling complexes by binding PKA regulatory subunits and coordinating interactions with lipogenic substrates including ACC1, PDHA, and ATGL 3. It also directly interacts with β2-adrenergic receptors and phosphodiesterases (PDE4D, PDE8A), modulating cAMP accumulation and downstream cardiac function 4. In cancer-associated fibroblasts, AKAP12 promotes macrophage M2 polarization via the PI3K/AKT/IL-34 axis, creating immunosuppressive tumor microenvironments 5. Clinically, AKAP12 dysregulation associates with multiple diseases. Downregulation correlates with cancer progression and metastasis through altered Src signaling and impaired VEGF-mediated neovascularization suppression 1, and reduced expression predicts poor prognosis in prostate cancer 6. Conversely, AKAP12 upregulation exacerbates heart failure via enhanced PDE8-mediated cAMP degradation 4 and alcohol-associated liver disease through disrupted PKA-dependent lipogenic control 3. AKAP12 serves as a diagnostic biomarker for fibromyalgia, correlating with CD8+ T cell infiltration 7.