PSMB1 (proteasome 20S subunit beta 1) is a non-catalytic structural component of the 20S proteasome core complex essential for protein homeostasis. As part of the 26S proteasome, PSMB1 participates in ATP-dependent degradation of ubiquitinated proteins, removing misfolded, damaged, or unnecessary proteins [UniProt]. It also associates with regulatory particles PA200 and PA28 to mediate ubiquitin-independent proteolysis in specialized pathways including spermatogenesis and MHC class I antigen generation [UniProt]. Mechanistically, PSMB1 regulates multiple signaling pathways: it binds and promotes proteasome-dependent degradation of onco-protein RAB34 to inhibit MEK/ERK signaling in colorectal cancer 1, and facilitates IKK-β degradation to suppress RANKL-induced osteoclast differentiation in ankylosing spondylitis 2. PSMB1 also negatively regulates antiviral immunity by promoting IKK-ε degradation, thus inhibiting RIG-I and TLR3 signaling during viral infection 3. Disease relevance includes associations with neurodevelopmental disorder with microcephaly, hypotonia, and absent language [NCBI], and identification as a downstream effector in idiopathic pulmonary fibrosis pathogenesis 4. Clinically, PSMB1 serves as an independent prognostic biomarker for colorectal cancer progression 1, with potential therapeutic implications through proteasome inhibitors or agents enhancing PSMB1 activity.