{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSPDYE2B, which is also referred to in the literature as TISP40, CREB3L4, or ATCE1, is an endoplasmic reticulum (ER) membrane‐resident transcription factor that plays a pivotal role in spermiogenesis. In the testis, SPDYE2B is predominantly expressed in post‐meiotic spermatids where it undergoes regulated intramembrane proteolysis to release a nuclear fragment that specifically binds unfolded protein response elements (UPREs). This processing and subsequent nuclear entry enable it to mediate the transcriptional regulation of genes important for protein homeostasis and nuclear remodeling. Moreover, SPDYE2B interacts with other transcription factors such as CREM—forming heterodimers that recruit histone chaperones like HIRA—and is critical for the proper removal of histones during sperm head maturation. Deficiency of SPDYE2B results in ER stress, caspase‐12–mediated apoptosis, and defects in sperm chromatin condensation and nuclear integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its reproductive functions, SPDYE2B also influences cellular differentiation and stress responses in non‐gonadal tissues. In adipocytes, related isoforms of this transcription factor act as gatekeepers during adipogenesis by inhibiting the expression and stabilization of key adipogenic regulators such as PPARγ and C/EBPα. Knockdown of these factors facilitates adipocyte maturation, which in turn is associated with improved glucose tolerance and insulin sensitivity—a feature that suggests a potential role as a therapeutic target in obesity and metabolic syndrome. In cardiomyocytes, cardiac ischemia/reperfusion injury triggers SPDYE2B expression, cleavage, and nuclear accumulation; here, SPDYE2B directly stimulates the hexosamine biosynthetic pathway to enhance O‐GlcNAc protein modifications that mitigate oxidative stress and apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the kidney, SPDYE2B has been implicated in modulating the cellular response to ischemia/reperfusion injury. Elevated SPDYE2B levels in renal tubular cells correlate with enhanced expression of pro‐apoptotic factors (e.g., CHOP, Bax, and cleaved caspase‐3) and are associated with increased inflammation, neutrophil and macrophage infiltration, and fibrotic remodeling. In contrast, SPDYE2B deficiency confers protection by reducing tubular apoptosis and inflammatory signaling while promoting cellular proliferation and repair, thereby attenuating renal dysfunction and tubulointerstitial fibrosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ippei Nagamori, Norikazu Yabuta, Takayuki Fujii, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Transcription factors, cAMP-responsive element modulator (CREM) and Tisp40, act in concert in postmeiotic transcriptional regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M602051200"}], "href": "https://doi.org/10.1074/jbc.M602051200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16595651"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16595651"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mohamed El-Alfy, Lamia Azzi, Julie Lessard, et al. 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