{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HSPA12A is a newly identified, atypical member of the Hsp70 family that appears to have diverse, context‐dependent functions in regulating cellular stress responses, development, metabolism, and disease progression. In the central nervous system, HSPA12A is highly expressed in neurons – particularly in frontal and occipital cortical regions – and its decreased expression has been associated with metabolic alterations in schizophrenia and with ischemic insults, suggesting an important role in neuronal protection and homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, HSPA12A has been implicated in hepatocellular carcinoma, where its overexpression promotes tumor growth and angiogenesis through physical interaction with proliferative cell nuclear antigen (PCNA) – facilitating its trimerization – and enhancing β‐catenin signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, its role appears to be tumor type–specific; while genetic variants in HSPA12A have been linked to a reduced risk of gastric cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", HSPA12A can promote migration in hepatocellular carcinoma cells by enhancing glycolytic activity and lactate export through increased membrane localization of monocarboxylate transporter 4 (MCT4)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in cancer, HSPA12A is also involved in developmental processes. Its expression has been noted during embryonic palate and limb formation, with altered mRNA levels correlating with congenital anomalies in these tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In metabolic regulation, HSPA12A participates in the browning of white adipose tissue in response to cold exposure and has been identified as a candidate gene affecting water‐holding capacity in beef cattle, thereby potentially influencing meat quality traits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, HSPA12A expression is modulated under conditions of inflammatory and environmental stress. Elevated hepatic and serum HSPA12A levels in patients with nonalcoholic steatohepatitis suggest a role in liver inflammatory responses"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and its altered expression in invertebrate as well as fish models indicates a conserved function in mediating immune responses and adaptation to environmental challenges."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, HSPA12A has been shown to contribute to the maintenance of mitochondrial integrity. In models of local anesthetic–induced myotoxicity, overexpression of HSPA12A protects skeletal muscle cells by preserving mitochondrial function via activation of PGC1α, highlighting its potential as a therapeutic target for mitigating drug-related muscle injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, the collective findings indicate that HSPA12A is a multifunctional chaperone involved in neuronal protection, cancer cell proliferation and migration, developmental processes, metabolic regulation, stress adaptation, and mitochondrial maintenance. Its pleiotropic roles across different tissues and species make HSPA12A a promising target for further investigation and potential therapeutic intervention in a range of pathologies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Julie L Pongrac, Frank A Middleton, Lansha Peng, et al. 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