Hoi1 targets the yeast BLTP2 protein to ER-PM contact sites to regulate lipid homeostasis

Here, we identify the conserved protein Ybl086c, which we name Hoi1 (Hob interactor 1), as an adaptor that targets the yeast BLTP2-like proteins Fmp27/Hob1 and Hob2 to ER-PM contact sites. Two separate Hoi1 domains interface with alpha-helical projections that decorate the central hydrophobic channel on Fmp27, and loss of these interactions disrupts cellular sterol homeostasis. The mutant phenotypes of BLTP2 and HOI1 orthologs indicate these proteins act in a shared pathway in worms and flies.

Together, this suggests that Hoi1-mediated recruitment of BLTP2-like proteins represents an evolutionarily conserved mechanism for regulating lipid transport at membrane contact sites.