An increasing number of both prokaryotic and eukaryotic cell types are being adapted as platforms for recombinant protein production. The overproduction of proteins in such expression systems leads to the formation of insoluble protein-based aggregates. Although these protein clusters have been poorly studied in most of the eukaryotic systems, aggregates formed in E. coli, named inclusion bodies (IBs), have been deeply characterized in the last decades. Contrary to the general belief, an important fraction of the protein embedded in IB is functional, showing promise in biocatalysis, regenerative medicine and cell therapy. Thus, the exploration of all these functional protein clusters would largely expand their potential in both pharma and biotech industry.