Casein is a milk protein emerging as a potential nanosystem for applications in therapy and diagnosis. Casein consists of four major phosphoproteins with their homologous primary amino acid sequences into the following families αs1, αs2, β, and κ-casein. In the aqueous phase, casein forms micelles binding with colloidal calcium phosphate. Biocompatibility, high drug binding/encapsulation capability, potential to cross the blood-brain barrier, and targeted cellular uptake are a few of the properties of casein micelles, enabling their application in therapy. This review discusses various components, properties, and functions of casein phosphoproteins and casein micelles. Application-specific cross-linking mechanisms and different synthesis approaches are also discussed. This review extensively explores casein's structural and functional properties and its biomedical application: targeted drug delivery and tissue engineering. The potential applications of casein-based complexes for treating iron deficiency anaemia and casein-derived peptides for inhibition of neuronal cognitive disorders are also discussed in this review. © 2022 Elsevier Ltd