A kinase anchoring protein (AKAP) 12 is a scaffolding protein that improves the specificity and efficiency of spatiotemporal signal through assembling intracellular signal proteins into a specific complex. AKAP12 is a negative mitogenic regulator that plays an important role in controlling cytoskeletal architecture, maintaining endothelial integrity, regulating glial function and forming blood-brain barrier (BBB) and blood retinal barrier (BRB). Moreover, elevated or reduced AKAP12 contributes to a variety of diseases. Complex connections between AKAP12 and various diseases including chronic liver diseases (CLDs), inflammatory diseases and a series of cancers will be tried to delineate in this paper. We first describe the expression, distribution and physiological function of AKAP12. Then we summarize the current knowledge of different connections between AKAP12 expression and various diseases. Some research groups have found paradoxical roles of AKAP12 in different diseases and further confirmation is needed. This paper aims to assess the role of AKAP12 in physiology and diseases to help lay the foundation for the design of small molecules for specific AKAP12 to correct the pathological signal defects.