{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nA series of investigations have delineated multifaceted roles for membrane proteins in regulating cellular homeostasis. Several studies have focused on the DNA damage‐regulated autophagy modulator (DRAM1), which is implicated in autophagy regulation and stress responses. For example, distinct p53‐inducible DRAM1 splice variants differentially localize to various organelles and modulate autophagy without triggering cell death."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, DRAM1 facilitates the efflux of amino acids from lysosomes to promote mTORC1 activation, thereby influencing growth, metabolism, and differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Other reports have highlighted the protective roles of DRAM1 in cerebral ischemia/reperfusion injury through promoting autophagosome–lysosome fusion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", in preeclampsia by enhancing mitophagy and preserving mitochondrial function"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", and in nonsmall‐cell lung carcinoma through accelerating EGFR endocytosis and lysosomal degradation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, DRAM1’s emerging role in inflammatory bowel disease"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", in orchestrating autophagy during stem cell differentiation via epigenetic modulation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", and in promoting the trafficking and acidification of mycobacteria‐containing vesicles for effective host defense"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "underscores its importance in cellular homeostasis and stress regulation.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to these findings on DRAM1, a distinct membrane protein, TMEM95, has been identified as a key mediator in the fertilization process. TMEM95 encodes a sperm acrosomal membrane protein whose absence leads to male-specific sterility in mice; notably, knockout sperm retain the ability to bind to, but fail to fuse with, the egg."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Detailed structural analysis revealed an evolutionarily conserved, positively charged region on TMEM95 that likely serves as a receptor-binding surface on the egg. Mutating amino acid residues within this region abolishes egg-binding activity, and monoclonal antibodies targeting TMEM95 significantly reduce sperm–egg fusion, despite the unaffected binding of sperm to eggs. These results collectively highlight that TMEM95 functions specifically to facilitate the membrane fusion step of fertilization through a receptor-mediated mechanism.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Li Yen Mah, Jim O'Prey, Alice D Baudot, et al. 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