Large-pore protein crystals (LPCs) are an emerging class of biomaterials. The inherent diversity of proteins translates to a diversity of crystal lattice structures, many of which display large pores and solvent channels. These pores can, in turn, be functionalized via directed evolution and rational redesign based on the known crystal structures. LPCs possess extremely high solvent content, as well as extremely high surface area to volume ratios. Because of these characteristics, LPCs continue to be explored in diverse applications including catalysis, targeted therapeutic delivery, templating of nanostructures, structural biology. This Feature review article will describe several of the existing platforms in detail, with particular focus on LPC synthesis approaches and reported applications.