{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIt is notable that none of the provided abstracts mention TMEM273. Instead, the collective literature focuses almost entirely on the CREB‐regulated transcription coactivator 2 (CRTC2, also known as TORC2) – a key mediator of cAMP‐dependent gene regulation that critically governs metabolic homeostasis. In the liver, for example, under fasting conditions CRTC2 becomes dephosphorylated and translocates into the nucleus where it partners with CREB to drive the transcription of gluconeogenic genes responsible for hepatic glucose production. In contrast, feeding‐related signals (via kinases such as AMPK, SIK2, and mTOR) promote CRTC2 phosphorylation, thereby restricting its nuclear entry and suppressing gluconeogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its hepatic role, CRTC2 is implicated in multiple tissues and cell types. In skeletal muscle and the central nervous system, it helps translate nutrient and hormonal cues to adjust energy expenditure and feeding behavior, while in pancreatic β‐cells it contributes to insulin secretion by coupling glucose sensing to CREB activity. In immune cells and adipocytes, CRTC2 (and related family members) modulate differentiation, cytokine production, and lipid metabolism via interactions with diverse signaling pathways and post‐translational modifications—including O‐glycosylation, ubiquitination, and binding to factors such as Pin1."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA number of studies also emphasize the therapeutic potential of targeting the CRTC2/CREB axis. Pharmacologic inhibitors, antisense oligonucleotides, or other genetic manipulations that dampen CRTC2 activity have been shown to improve hyperglycemia, ameliorate lipid abnormalities, and even mitigate the progression of non‐alcoholic fatty liver disease and polycystic kidney disease. In addition, innovative work has demonstrated that modulation of CRTC2 can affect phase‐separation dynamics within the nucleus to activate transcription elongation of specific gene sets, thereby linking cAMP signaling to broader transcriptional programs across tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "40"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Seung-Hoi Koo, Lawrence Flechner, Ling Qi, et al. 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