{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPSMA6 encodes the proteasome subunit α type 6, a crucial component of the 20S proteasome core complex that mediates the regulated degradation of ubiquitinated proteins and thereby influences key cellular signaling pathways such as NF‐κB. Functional studies have demonstrated that specific promoter variants—for example, the –8C/G single nucleotide polymorphism—increase PSMA6 transcription, modulating proteasomal activity and inflammatory responses implicated in myocardial infarction and other disorders. This central role in proteostasis underscores PSMA6’s contribution to normal cellular function and stress responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nExtensive genetic association studies across diverse populations have implicated PSMA6 variants in a spectrum of cardiometabolic and inflammatory disorders. Investigations in Japanese, Chinese, Caucasian, Saudi, Latvian, Finnish, and Ukrainian cohorts have examined the –8C/G polymorphism and related haplotypes in relation to myocardial infarction, coronary artery disease, hypertension, and diabetes (both type 1 and type 2), as well as inflammatory conditions such as psoriasis. Although certain cohorts have reported significant associations—with risk alleles leading to increased PSMA6 expression and altered NF‐κB signaling—other studies have found no significant associations, suggesting that the contribution of PSMA6 to disease susceptibility may be context‐dependent. Together, these findings reveal a multifaceted role for PSMA6 in modulating proteasomal degradation with downstream effects on inflammation and metabolic regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in cardiometabolic and inflammatory contexts, aberrant PSMA6 expression has emerged in the oncology and renal fields. In lung cancer, for instance, semi-genome-wide shRNA screening and copy number analyses have identified recurrent amplifications and elevated expression of PSMA6, with experimental silencing resulting in apoptosis and G2/M cell cycle arrest in cancer cell lines—highlighting its potential as a therapeutic target. Conversely, in diabetic nephropathy, PSMA6 protein is notably downregulated in renal tissues, with post-transcriptional regulation by specific microRNAs contributing to altered proteasomal function that may exacerbate kidney damage. These findings illustrate that deregulation of PSMA6 can have profound consequences, either by sustaining a proliferative oncogenic state or by impairing normal cellular homeostasis in chronic metabolic disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kouichi Ozaki, Hiroshi Sato, Aritoshi Iida, et al. 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