The construction of functional, synthetic microcompartments is crucial for advancing our understanding of cellular processes and enhancing technological applications across various fields. This study introduces the creation of lipoproteinosomes, which are microscale compartments constructed from bovine serum albumin and stearoyl chloride (BSA-SC) nanoconjugates synthesized by employing thiourea-linkage chemistry. These spherical lipoproteinsomal microcapsules are formed through a water-in-oil Pickering emulsification process and stabilized in aqueous environments by cross-linking. The microcapsules not only exhibit capabilities to encapsulate and retain water-soluble macromolecules but also display enzyme-driven communication as protocells. This research not only underscores the potential of using natural amphiphilic compounds for constructing microcompartments but also highlights their broad applicability in biomedicine, protocell research, and microreactor technology.