A Druggable G Protein Checkpoint in Cholesterol Efflux
Statins slow but rarely reverse plaque burden, leaving residual risk driven by LAM dysfunctionGIV (CCDC88A) non-canonically modulates Gαi to suppress macrophage cholesterol effluxGIV loss or inhibition restores ABCA1 activity via transcriptional and post-translational controlBlocking the GIV●Gαi checkpoint defats LAMs, regresses plaques, and relieves systemic lipid overloadIdentifies a druggable node that redefines RCT restoration as a therapeutic paradigm in immunometabolic disease.
Authors
- Vanessa Castillo (ORCID: https://orcid.org/0000-0002-4182-8846)
- Saptarshi Sinha (ORCID: https://orcid.org/0000-0003-0687-924X)
- Gajanan D. Katkar (ORCID: https://orcid.org/0000-0002-9982-8582)
- Jerry Yang (ORCID: https://orcid.org/0000-0002-8423-7376)
- Stephanie Lissette Peñate Aviles
- Benedikt Kaufmann (ORCID: https://orcid.org/0000-0002-8141-9676)
- Pradipta Ghosh
- Megan L. Estanol
- Caroline Biggs
- Michelle Nacayama
- Ella McLaren
- Ellie Tam
- Raktim Mukharjee
- Mahitha Sree Anandachar
- Shu-Tsing Hsu
Institutions
- University of California San Diego (US)
- Human BioMolecular Research Institute (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-02-17
- DOI
- https://doi.org/10.64898/2026.02.15.705962
- Primary Topic
- Cholesterol and Lipid Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.00