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

Steroidogenic acute regulatory protein-related lipid transfer protein 3 (STARD3), also known as MLN64, is a late endosomal membrane protein that plays a critical role in intracellular cholesterol transport [1]. It facilitates the non-vesicular movement of cholesterol from endosomes to the endoplasmic reticulum by forming membrane contact sites through interactions with VAP proteins [2]. STARD3 is frequently overexpressed in HER2-positive breast cancers due to its location on the 17q12-21 amplicon, where it promotes tumor cell proliferation by ensuring a steady supply of cholesterol for membrane synthesis and signaling [3]. While no drugs targeting STARD3 are currently FDA-approved, it is considered a promising therapeutic target for specific cancer subtypes and metabolic disorders [3]. Research focuses on small molecule inhibitors that disrupt its lipid-binding START domain or its ability to form contact sites to starve cancer cells of essential lipids [4]. Targeting STARD3 may provide a synergistic effect when combined with HER2-targeted therapies in resistant breast cancer cases [3]. Beyond oncology, its role in lipid trafficking makes it a subject of interest in neurodegenerative and metabolic research [2]. The protein's unique structure, containing both a MENTAL domain for membrane anchoring and a START domain for lipid binding, allows it to bridge organelles effectively [1]. References: [1] UniProt (Q14849); [2] Alpy et al. (2013) Nat Comm; [3] Sripada et al. (2021) BBA-Rev Cancer; [4] Wilhelm et al. (2017) BMC Biol.

Other names

Metastatic lymph node 64 proteinMLN64CAB1StAR-related lipid transfer protein 3

Inhibition of endosomal cholesterol transport and disruption of membrane contact sites between late endosomes and the endoplasmic reticulum.