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In a new PNAS study published on September 22, 2026, scientists at Scripps Research engineered a small synthetic protein that can bind to TLR4 within cell membranes and block subsequent inflammatory responses. The findings advance understanding of what TLR4’s membrane-embedded region does: rather than a passive anchor, it’s an active determinant of cross-membrane signaling—mechanistic insight that could guide design of a new class of anti-inflammatory treatments. More broadly, the study outlines new computational tools that other researchers can use to target proteins within membranes.