PSMC6 encodes a critical ATPase subunit of the 26S proteasome complex that plays essential roles in protein homeostasis and cellular regulation. As part of the heterohexameric AAA+ ATPase ring, PSMC6 facilitates ATP-dependent unfolding and degradation of ubiquitinated proteins 1. The protein demonstrates significant clinical relevance across multiple cancer types, serving as a diagnostic biomarker in colorectal cancer where it contributes to an extracellular vesicle-based detection panel with >97% accuracy 2. In ovarian carcinoma, elevated PSMC6 levels correlate with advanced tumor stages, reduced progression-free survival, and cisplatin resistance through ERK1/2 pathway modulation 1. PSMC6 also interacts with SYT4 in gastric cancer to activate Wnt/β-catenin signaling, promoting malignant progression 3. Beyond oncology, PSMC6 genetic variants show sex-specific associations with juvenile idiopathic arthritis subtypes and influence plasma proteasome levels 4. In pulmonary arterial hypertension, PSMC6 mediates noncanonical MST signaling by facilitating FOXO3 downregulation, supporting pathological vascular cell proliferation 5. Additionally, PSMC6 variants are associated with multiple sclerosis susceptibility and treatment response in certain populations 6, highlighting its broad involvement in immune-mediated diseases and cancer pathogenesis.