Role of STARD4 and NPC1 in intracellular sterol transport
Bibliographic record
Abstract
Cholesterol plays an important role in determining the biophysical properties of membranes in mammalian cells, and the concentration of cholesterol in membranes is tightly regulated. Cholesterol moves among membrane organelles by a combination of vesicular and nonvesicular transport pathways, but the details of these transport pathways are not well understood. In this review, we discuss the mechanisms for nonvesicular sterol transport with an emphasis on the role of STARD4, a small, soluble, cytoplasmic sterol transport protein. STARD4 can rapidly equilibrate sterol between membranes, especially membranes with anionic lipid headgroups. We also discuss the sterol transport in late endosomes and lysosomes, which is mediated by a soluble protein, NPC2, and a membrane protein, NPC1. Homozygous mutations in these proteins lead to a lysosomal lipid storage disorder, Niemann-Pick disease type C. Many of the disease-causing mutations in NPC1 are associated with degradation of the mutant NPC1 proteins in the endoplasmic reticulum. Several histone deacetylase inhibitors have been found to rescue the premature degradation of the mutant NPC1 proteins, and one of these is now in a small clinical trial.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".