The catalytic core of the proteasome contains three pair of catalytic subunits that perform distinct proteolytic activities referred to as caspase-like, trypsin-like, and chymotrypsin-like. In the standard proteasome, the catalytic subunits are β1, β2, and β5. These subunits can be replaced in nascent proteasomes by the subunits LMP2 (β1i), MECL-1 (β2i), and LMP7 (β5i), which form the core of the immunoproteasome. The immunoproteasome is a proteasome subtype that is abundant in immune cells and also present, albeit in low concentrations, in cells outside the immune system. A well-described function of immunoproteasome is to generate peptides for MHC class I for display on the cell surface. Functions of immunoproteasome that go beyond its role in generating antigenic peptides are emerging from studies in immunoproteasome-deficient mice and from human diseases linked to mutations in immunoproteasome subunits. Notably, oxidative stress and pro-inflammatory cytokines, conditions that predominate in retinal diseases, are associated with immunoproteasome upregulation. Multiple methods used to investigate immunoproteasome function in the retina and in cultured retinal pigment epithelial cells will be discussed in detail.