{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BCL2L13 (also known as Bcl‐rambo) is a multifunctional member of the Bcl‑2 family that plays diverse roles in mitochondrial homeostasis and cell fate determination. In mammalian cells, BCL2L13 functions as a mitophagy receptor homologous to yeast Atg32 by binding LC3/GABARAP proteins to promote mitochondrial fragmentation and the selective clearance of damaged mitochondria. Notably, it can trigger mitochondrial fission independently of the canonical fission machinery and cooperates with the ULK1 complex to initiate mitophagy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in mitochondrial quality control, BCL2L13 exerts context‐dependent effects on apoptosis. In some cancer models such as glioblastoma and pediatric acute lymphoblastic leukemia, elevated BCL2L13 expression is associated with resistance to therapy and poorer outcomes, suggesting it can inhibit apoptosis by interacting with mitochondrial proteins like adenine nucleotide translocators and voltage‐dependent anion channels to modulate caspase activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " By contrast, in breast cancer, higher levels of the proapoptotic BCL2L13 correlate with improved prognosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and experimental studies in model systems, including Drosophila and cultured human cells, have demonstrated that BCL2L13 can promote effector caspase activation and mitochondrial permeabilization."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n BCL2L13 activity is also implicated in non‐cancerous cellular processes. During adipocyte differentiation and the browning of white adipose tissue, increased expression of BCL2L13 is linked with enhanced mitochondrial fusion, biogenesis, and metabolic reprogramming."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Furthermore, in neurons and chondrocytes, BCL2L13 is targeted by specific microRNAs (for example, miR‑484 in neurons and miR‑141‑3p in chondrocytes) to modulate caspase‑3 activity and cytochrome c release; such regulation influences the cellular response during ischemia/reperfusion injury and osteoarthritis, respectively."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, alternative splicing of the BCL2L13 transcript—for example, the generation of a BH4‑only isoform (Bcl‑rambo β) lacking classical BH domains—further diversifies its functional repertoire, potentially altering its apoptotic and subcellular targeting properties."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, BCL2L13 acts as a critical regulator of mitochondrial turnover through mitophagy and modulates apoptosis in a context‐dependent manner. Its versatile functions have significant implications in cancer therapy resistance, metabolic reprogramming during adipocyte differentiation, and the responses of neural and chondrocyte lineages to injury.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tomokazu Murakawa, Osamu Yamaguchi, Ayako Hashimoto, et al. 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