Amphipathic helices repurpose a Patched/NPC1-like cholesterol transporter to function at Plasmodium-erythrocyte membrane contact sites.

Amphipathic helix-linker-helix domains repurpose PfNCR1, a Patched/NPC1-like cholesterol transporter in Plasmodium falciparum, to localize to 3–4 nm membrane contact sites.

• Why it matters: The parasite–erythrocyte interface includes narrow contact sites that mediate lipid exchange and export, but the resident machinery and how it accesses this space are poorly defined.
• What they did: Live-cell microscopy and cholesterol homeostasis assays show that an HLH modification is necessary for efficient PfNCR1 localization, and a GPI-anchored fluorescent reporter reveals the HLH is sufficient.
• The result: Correct localization is required for maintaining low cholesterol levels, and targeting depends on HLH amphipathicity rather than a specific primary sequence, supporting physicochemical partitioning for contact-site targeting.

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