8.A.120.3.1
STAR-related lipid transfer protein, STARD4, of 205 aas and 0 TMSs.  It is involved in the intracellular transport of cholesterol; it binds cholesterol or other sterols (Rodriguez-Agudo et al. 2008). Xie and Weinstein 2025 presented a quantitative model of the allosteric molecular mechanisms of selective cholesterol (CHL) uptake and delivery by the StarD4 protein - an intracellular cholesterol trafficking protein that facilitates the crucial non-vesicular sterol transport between the plasma membrane and the endoplasmic reticulum. This sterol-specific transfer protein is essential for maintaining the healthy life of human cells. In its physiological function, StarD4 targets both sterol donor and acceptor membranes via interactions with anionic lipids. Experiments have illuminated the kinetics of this sterol transfer and showed it to be modulated by specific phosphatidylinositol phosphates (PIPs) on the target membrane.  The specific molecular mechanism for recognizing PIP2-subtypes in membranes by StarD4 couples to the defined allosteric pathway that induces the CHL binding pocket to propagate the signal for either uptake or release of the sterol. The central role determined for allostery in these significant advances in the understanding of intracellular cholesterol trafficking by StarD4, aligns with experimentally determined properties of StarD4 function, and interprets them in experimentally testable atomistic terms that explain function-altering results of mutations (Xie and Weinstein 2025).