Proteasome subunit beta type-5

PSMB5 encodes proteasome subunit beta type-5, a core catalytic component of the 20S proteasome complex that displays chymotrypsin-like proteolytic activity (UniProt: P28074). When associated with 19S regulatory particles to form the 26S proteasome, it mediates ATP-dependent degradation of ubiquitinated proteins, maintaining protein homeostasis by removing misfolded or damaged proteins. The protein also participates in ubiquitin-independent proteolysis when associated with PA200 or PA28 regulatory particles, with roles in spermatogenesis and MHC class I antigen presentation.

PSMB5 functions broadly in protein quality control across cellular compartments. The UniProt record lists no explicit disease annotations (UniProt: P28074), though proteasomal dysfunction is implicated in multiple neurodegenerative contexts.

In Alzheimer's disease, PSMB5 is significantly downregulated in post-mortem AD brain relative to age-matched controls (mean log2FC: −0.54; Chaparral AD proteomics). This reduction in proteasomal capacity may compromise the clearance of misfolded proteins, including amyloid-beta and tau aggregates, potentially contributing to pathogenic protein accumulation characteristic of AD neurodegeneration.