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Interestingly, PNPLA3 I148M is not properly targeted by the UPS which likely promotes the disease-causing variant to accumulate on LDs (135) where it can disrupt protein-protein interactions critical for TAG hydrolysis (70, 75)

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The second is dose and route translation : even where an effect is real in a mouse, the human-equivalent dose is not a simple body-weight scaling, and as the route section above stressed there is no human bioavailability figure to anchor an oral-versus-injected comparison

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