PSMB11 encodes β5t, a thymus-specific catalytic subunit of the thymoproteasome that is essential for CD8+ T cell development. The thymoproteasome is a specialized 20S proteasome expressed exclusively in cortical thymic epithelial cells (cTECs) that generates a distinct set of MHC class I-bound peptides required for positive selection of functionally competent CD8+ T cells 1. PSMB11 arose through tandem duplication from PSMB5 in early jawed vertebrates and remains intronless, representing a unique evolutionary adaptation 2. Mechanistically, β5t reduces the chymotrypsin-like activity of the standard proteasome compared to its homologs PSMB5 and PSMB8, creating a specialized peptide repertoire that shapes T cell selection 3. PSMB11 expression is tightly regulated as a FOXN1 target gene in cTECs, and FOXN1 haploinsufficiency reduces PSMB11 expression and CD8+ T cell production 4. Genetic variations in PSMB11 significantly impact human health. Common human polymorphisms alter β5t amino acid sequences, reducing protein processing and CD8+ T cell cellularity in homozygotes, though severe health problems are rare 1. Computationally, PSMB11 is highly enriched for functional variants; specific polymorphisms impair CD8+ T cell development in vivo and associate with increased autoimmune disease risk 5, suggesting proteasome variations complement MHC haplotypes in determining individual susceptibility to autoimmunity.