The present invention provides methods and compositions for treatment of diseases and disorders. More specifically, the invention for the first time shows a link between IRAK-1 and phosphorylation of proteins involved in cardiovascular disease, diabetes, neurodegeneration, and associated diseases and disorders and complications. Typically, the diseases and disorders involve an inflammatory component. Assays for bioactive substances affecting IRAK-1 regulated progression of inflammation and diseases and disorders involving inflammation are also disclosed.