GRAMD1B is a non-vesicular cholesterol transporter that mediates the movement of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER), playing a critical role in cholesterol homeostasis 1. The protein contains a GRAM domain that senses "accessible" cholesterol and anionic lipids (such as phosphatidylserine) at the PM, and a StART-like domain that facilitates cholesterol extraction and transport 1. GRAMD1B functions at ER-PM contact sites, where it is recruited in response to increased PM cholesterol levels and works coordinately with NPC1 to regulate cholesterol egress from endocytic organelles 2. In intestinal enterocytes, GRAMD1B (Aster-B) is essential for non-vesicular cholesterol movement downstream of NPC1L1, with GRAMD1B-deficient mice showing impaired dietary cholesterol absorption and protection against diet-induced hypercholesterolemia 3. In the nervous system, GRAMD1B is implicated in neuroinflammatory and neurodegenerative diseases; it is upregulated in Alzheimer's disease and frontotemporal lobar degeneration models, where it increases free cholesterol accumulation and impairs autophagy flux, ultimately promoting phosphorylated tau accumulation 4. Additionally, GRAMD1B variants have been associated with multiple sclerosis susceptibility and serum lipid levels 56. The GRAM domain has been engineered as a biosensor (GRAM-W) to visualize accessible cholesterol dynamics in live cells 7.