Target intelligence / Profile preview

Steroidogenic acute regulatory protein-related lipid transfer domain containing 3 (STARD3) (STARD3)

Target
STARD3
Molecular classification
Lipid transfer protein, START domain-containing protein family
01

Overview

Steroidogenic acute regulatory protein-related lipid transfer domain containing 3 (STARD3), also known as MLN64, is a late endosomal membrane protein that plays a critical role in non-vesicular cholesterol transport [UniProt P56191]. It functions by creating membrane contact sites between the endoplasmic reticulum and late endosomes, facilitating the direct transfer of cholesterol via its conserved START domain [PubMed: 25231981]. In a physiological context, STARD3 maintains the lipid composition of endocytic compartments, which is vital for proper cellular trafficking and signaling [PubMed: 26074567]. Pathologically, STARD3 is frequently overexpressed in HER2-positive breast cancers due to its location on the 17q12 chromosomal amplicon [PubMed: 23536713]. This overexpression leads to increased cholesterol accumulation in endosomes, which promotes tumor cell proliferation and provides a survival advantage to cancer cells [PubMed: 26919241]. Consequently, STARD3 is emerging as a promising therapeutic target, with research focusing on small molecule inhibitors designed to disrupt its cholesterol-binding capacity and impair oncogenic growth [PubMed: 32824815].

Other names
MLN64Metastatic lymph node 64 proteinCAB1StAR-related lipid transfer domain-containing protein 3
02

Mechanism of action

Inhibition of non-vesicular cholesterol transport between the endoplasmic reticulum and late endosomes to disrupt oncogenic signaling and membrane integrity in cancer cells [PubMed: 32824815].

03

Biological functions

Cholesterol transportLipid metabolismEndosomal traffickingMembrane contact site formation
04

Disease associations

Breast cancerGastric cancerProstate cancerAtherosclerosis
05

Safety considerations

Disruption of systemic or cellular cholesterol homeostasisPotential off-target effects on other START domain proteinsPotential impact on steroidogenesis pathways
06

Interacting drugs

Experimental STARD3 inhibitors

1 more in the full profile.

07

Biomarkers

STARD3 protein expressionSTARD3 mRNA levelsHER2/ERBB2 co-amplification

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