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More critically, the human population exhibits three distinct ApoE isoforms with markedly divergent LDLR-binding properties, humans exhibit three isoforms (ApoE2, ApoE3, ApoE4) with markedly different LDLR-binding affinities: ApoE2 binds to LDLR with 50- to 100-fold weaker affinity than ApoE3 or ApoE4, potentially impairing LNP uptake in ApoE2 carriers [142]